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

IVUS analysis of the acute and long-term stent result using motorized pullback: intraobserver and interobserver variability.

Intravascular ultrasound imaging has become an established method for analysis of intra-coronary stents. We analyzed the reproducibility of morphometric measurements immediately and late after stent implantation and the variability in the selection of predefined sites during motorized catheter pullback. Fifty consecutive patients were investigated immediately and 6 months after Palmaz-Schatz stent implantation (motorized catheter pullback 0.5 mm/sec; 2.9 Fr; 30-MHz transducer). Two experienced investigators independently identified the proximal and distal reference, stent inlet, stent outlet, and the minimal in-stent area in each imaging run. The longitudinal distance between corresponding measurement sites was calculated. Lumen, stent, and vessel area were assessed by planimetry, mean difference was calculated. Long-term reproducibility was analyzed by comparison of measurements made at predefined sites within the stent, immediately and late after implantation. Observer agreement in identification of predefined measurement sites was high. Longitudinal distance between corresponding measurement sites was low and pronounced for the minimal in-stent lumen area. Variabilities for the intra- and interobserver comparison were similar. Values for interobserver comparison were given in brackets. Acute after stent implantation, the variability for the reference proximal was 4.9% (0.4%), distal -1.0% (-4.2%), minimal in-stent lumen -0.5% (1.3%). At follow-up, variability for the reference proximal was -11.0% (-2.2%), distal -1.0% (-2.3%), minimal in-stent lumen 1.9% (6.1%). Long-term reproducibility for the proximal stent inlet was 2.7% (observer 1) and -0.4% (observer 2), for the distal stent outlet 1.3% (observer 1), -3.0% (observer 2), respectively. IVUS investigations with motorized IVUS pullback in stented coronary segments show a low intra- and interobserver variability, both immediately and late after stent implantation. Absolute and relative area differences are low. Long-term reproducibility of measurements within predefined stent sites was high. Motorized catheter pullback guarantees high reliability of IVUS measurements and should be routinely used for clinical IVUS studies.

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.

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.

Impact of target lesion calcification on coronary stent expansion after rotational atherectomy.

BACKGROUND: Calcified lesions carry the risk of suboptimal stent expansion. The purpose of this study was to investigate the impact of target lesion calcification on intracoronary ultrasound (ICUS) guided stent expansion after rotational atherectomy. METHODS: Stent expansion was assessed by ICUS in 39 patients with the aid of the proximal stent/proximal reference lumen, the minimal stent/mean reference lumen, and the minimal stent/minor reference lumen ratios as well as the symmetry index. Thirty-nine stent implantations in uncalcified lesions served for comparison. RESULTS: Relative stent expansion ranged between 76.3% +/- 6.7% and 98.4% +/- 16.4%. Categorization according to an ICUS-derived arc of superficial lesion calcium of <180 degrees (average 102 +/- 74 degrees) or >180 degrees (average 248 +/- 71 degrees) revealed decreased stent symmetry in calcified lesions >180 degrees compared with the control group (P <.05). Despite a trend toward less expansion with increasing calcium load, no significant differences of the lumen area ratios between the study groups was present. CONCLUSION: Rotational atherectomy before ICUS-guided stent implantation enables adequate stent expansion even in significant superficial target lesion calcification.

Epicardial intimal thickening in transplant coronary artery disease and resistance vessel response to adenosine: a combined intravascular ultrasound and Doppler study.

BACKGROUND: Transplant coronary artery disease is the major factor limiting long-term survival after cardiac transplantation. Both intravascular ultrasound imaging (IVUS) and intracoronary flow studies have been used to assess the morphologic and functional importance of the disease. However, the impact of epicardial intimal thickening, as quantitated by IVUS, on the resistance vessel response to adenosine has not been explored. METHODS AND RESULTS: Seventy-six coronary arteries without angiographically overt coronary disease (diameter stenosis visually, < or =50%) were studied with both IVUS and intracoronary Doppler in 54 patients 0.5 to 127 months after transplantation. Mean intimal index and mean lumen cross-sectional area (CSA) were determined by IVUS, and the average was obtained for every coronary artery. Coronary flow average peak velocity (APV) was obtained by Doppler before and after administration of 16 microg adenosine to calculate coronary flow velocity reserve (CFVR) and coronary vascular resistance index (CVRI). The hyperemic pressure-flow velocity ratio (hyperemic mean aortic pressure/hyperemic APV) as an index of minimal coronary resistance was further derived. The intimal index (mean, 20.0+/-10%) did not correlate with either CFVR (mean, 2.9+/-0.7, r=.12) or CVRI (mean, 0.33+/-0.1, r=.16). However, a significant correlation between the intimal index and the hyperemic pressure-flow velocity ratio (mean, 1.52+/-0.47 mm Hg/cm/s, r=.74, P<.0001) was found. The hyperemic pressure-flow velocity ratio was not influenced by the presence or absence of left ventricular hypertrophy or a mild acute rejection period (International Society for Heart and Lung Transplantation grades IA and IB). CONCLUSIONS: This study shows that in patients without angiographically overt coronary disease, the degree of epicardial intimal thickening as quantified by IVUS did not predict the adenosine vasodilator response, when determined by commonly used parameters such as CFVR and CVRI. The hyperemic pressure-flow velocity ratio best reflected the functional significance of transplant coronary artery disease.

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.

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.

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.

Coronary plaque morphologic characteristics early and late after heart transplantation: in vivo analysis with intravascular ultrasonography.

To characterize plaque morphologic characteristics of transplant coronary artery disease early and late after cardiac transplantation, 72 patients were studied with intravascular ultrasonography during routine coronary angiography (group 1, 25 patients < or = 2 months after surgery; group 2, 47 patients > or = 12 months after surgery). Both groups had comparable baseline characteristics. Three hundred fifty-one segments were imaged in 127 coronary arteries (4.9 +/- 1.8 segments per patient). By intravascular ultrasonography, relevant intimal thickening (> 0.3 mm) was found in the majority of patients (68% for group 1 and 72% for group 2). Angiography detected abnormal findings in only 16% and 32% for groups 1 and 2, respectively. Mean intimal index was higher in patients late after transplantation (27% +/- 12% vs 17% +/- 12%, respectively; p < 0.01). Maximal and mean plaque thickness were comparable in both groups, whereas a higher mean plaque circumference was found in group 2 (278 +/- 66 degrees vs 211 +/- 75 degrees, respectively; p < 0.002). The lesions were more eccentric in patients early after transplantation (mean eccentricity index 95% +/- 7% vs 77% +/- 15%, respectively; p < 0.0001). Diffuse, concentric intimal thickening was not a common pattern. Maximal plaque thickness correlated with donor age (r = 0.50, p < 0.0001). Coronary lesions were frequent even early after transplantation, with predominantly eccentric plaque morphologic characteristics indicative of preexisting atherosclerosis. Later after transplantation, a more homogeneous plaque distribution was seen, partly with diffuse concentic intimal thickening. Late transplant coronary artery disease appears to be a combination of preexisting native and acquired immune-mediated coronary artery disease.

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.

[Quantitative dobutamine stress echocardiography in follow-up of heart transplantation: normal values and findings in patients with transplant vasculopathy]. / Quantitative Dobutamin-Stressechokardiographie in der Spätphase nach Herztransplantation: Normwerte und Befunde bei Patienten mit Transplantatvaskulopathie.

Cardiac allograft vasculopathy (CAV) remains a major problem after heart transplantation. This prospective study was performed to analyze the value of quantitative dobutamine stress echocardiography for the diagnosis of CAV compared with coronary angiography and intravascular ultrasound (IVUS). In 80 patients late (> or = 12 months) after cardiac transplantation, a total of 144 studies were evaluated. In addition to the usually performed regional wall motion analysis of 2D-echocardiograms, systolic thickening of septum and left ventricular posterior wall was quantified by M-mode echocardiography. In patients with CAV by invasive angiography and/or IVUS, systolic thickening of the septum and posterior wall was significantly lower at rest and at maximum dobutamine infusion than in patients without CAV. From a subgroup of 23 studies in transplant recipients without TVP or other cardiac complications, normal values for the M-mode parameters were calculated. The lower limits were: systolic thickening of septum at rest, > 17.2%, at maximum stress, > 45.9%; systolic thickening of left ventricular posterior wall at rest, > 41.6%, at maximum stress, > 67.6%. Regional wall motion analysis of 2D-echocardiograms had a sensitivity of 76% (specificity 82%) for diagnosis of CAV defined by invasive methods, evaluation of wall thickening by M-mode alone had a sensitivity of 63% (specificity 76%). The combined 2D- and M-mode-echocardiographic analysis yielded a sensitivity of 85% (specificity 71%). In summary, dobutamine stress echocardiography is a useful method for the noninvasive diagnosis of CAV. The quantitative M-mode analysis improves the sensitivity of the 2D-analysis. The calculated normal values for the M-mode parameters in heart transplant recipients may serve as reference for other studies.

[Prospective study of the frequency and extent of donor-transmitted coronary disease after heart transplantation by intravascular ultrasound]. / Prospektive Untersuchung von Häufigkeit und Ausmass spenderbedingter koronarer Herzkrankheit nach Herztransplantation mit intravaskulärem Ultraschall.

PROBLEM AND OBJECTIVE: Cardiac allograft vasculopathy influences long-term survival of patients after heart transplantation. Donor-transmitted coronary artery disease may contribute to the further development of cardiac allograft vasculopathy. The aim of this study was to characterize by intracoronary ultrasound the extent and frequency of transmitted coronary artery disease. PATIENTS AND METHODS: Intravascular ultrasound studies were performed at routine angiography in 33 patients (26 men, 7 women, mean age 51 [23-69] years) early after heart transplantation. Plaque morphology was analysed in 153 coronary segments of 52 epicardial coronary arteries. RESULTS: Relevant atherosclerosis (defined as maximal plaque thickness > or = 0.5 mm in at least one coronary segment) was found in 17 patients (52%), while angiography showed irregularities in only 7 patients (21%). Maximal plaque thickness in patients with relevant atherosclerosis was 1.13 +/- 0.32 mm, mean plaque index was 19.2 +/- 10.2%. Plaque formation was eccentric, and plaques were predominantly located in proximal segments. Morphologic changes affecting more than one segment were found in 52% of the patients. Comparing clinical factors, only donor age predicted the degree of atherosclerosis. CONCLUSIONS: In more than one half of the patients studied early after heart transplantation, Intravascular ultrasound revealed epicardial atherosclerotic lesions which were incompletely identified by coronary angiography. The degree of atherosclerosis was closely related to donor age. The potential influence of donor transmitted coronary artery disease on the progression of transplant coronary artery disease requires further longitudinal 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.

[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.

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.

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.

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.