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Unlabelled: Fractional flow reserve (FFR) is a new but well established parameter for the hemodynamic evaluation of coronary stenoses. A FFR below 0.75 was validated as functionally significant in coronary one or two vessel disease. This study was designed to prospectively define the best FFR cut off value (BCV) in patients with multivessel disease using two noninvasive tests, myocardial perfusion scintigraphy (SPECT) and contrast-enhanced dobutamine stress echocardiography (DSE) as reference methods., Methods: 47 symptomatic patients (29 male, mean age 64+/-10 yrs) with angiographically intermediate coronary lesions (50-75% diameter stenosis) entered the study. DSE (5-40 microg/min/kg dobutamine) was performed after intravenous injection of a second generation transpulmonary contrast agent. SPECT (Tc-99m-MIBI) was done at peak stress. All tests (DSE, SPECT and FFR) were performed within 4 weeks., Results: SPECT yielded positive results in 15 and DSE in 16 patients, respectively. Mean FFR measured in the target lesion (RCA n=10; LAD n=22, RCX n=15) was 0.80+/-0.13. FFR was <0.75 in 15 patients. By performing a ROC analysis the BCV (highest sum of sensitivity and specificity) was found at 0.75. At this cut off value using both non-invasive tests as reference method, sensitivity and specificity were 83 and 77%., Conclusion: In patients with multivessel disease, a FFR <0.75 identifies a hemodynamically relevant lesion as compared to DSE and SPECT. This study underlines that FFR criteria are also applicable in patients with complex coronary artery disease.

In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to a high incidence of recurrent restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. Inhibition of neointima formation has been regarded as the relevant mechanism of action. Yet, positive remodelling has been suspected as another contributing factor. Since only very few precise analyses of the extent, distribution and time course of the respective mechanims exist, the goal of the present study was to describe the changes of the vessel geometry at the target lesion and at the reference site following angioplasty and VBT of ISR in 42 patients by means of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) before and after the index procedure and at the 3 and 6 month follow-up. By QCA the acute lumen gain measured 2.2+/-0.8 mm, the late lumen loss at 3 months was 0.1+/-0.5 mm and at 6 months 0.4+/-0.7 mm. By IVUS luminal cross-sectional area increased from 1.5+/-1.2 mm(2) to 7.9+/-1.9 mm(2) (p<0.001). The intima hyperplasia cross-sectional area at 3 months was only 0.2+/-1.0 mm(2) (p=0.191), but increased to 0.7+/-0.6 mm(2) (p<0.001) at 6 months resulting in a lumen cross-sectional area of 7.1+/-1.7 mm(2). Stent dimensions did not show any significant changes over time. The external elastic membrane cross-sectional area at 3 months increased by 1.3+/-1.9 mm(2) (p<0.001), and showed a further increase by 0.7+/-2.9 mm(2) at 6 months. Positive remodelling could be demonstrated also at the reference segment. In conclusion the absolute amount of intima hyperplasia during a 6-month follow-up period after VBT of ISR is low and most pronounced between the third and sixth month. Besides this, predominantly within the first 3 months of follow-up, significant positive remodelling could be demonstrated at the target lesion and at the reference site. Both observed effects may contribute to the preservation of the vessel lumen.

Background: Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. Therefore, achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of FFR. The study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilatation of the coronary microcirculation when high doses are used, resulting in a more accurate FFR measurement., Methods: Thirty-six patients with 43 moderate lesions underwent determination of FFR during cardiac catheterization. FFR was calculated in all lesions as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (16, 24, 32 and 40 microg for both coronary arteries) were administered in a randomized fashion., Results: No adverse events occurred with any intracoronary adenosine bolus. At baseline there were no significant differences for mean aortic and distal coronary pressure, heart rate as well as FFR values between the different doses. FFR was not significantly altered from the different incremental adenosine doses. However, in 27 (63%) out of 43 lesions there was a further reduction of FFR up to 0.23 when a dose >16 microg was injected., Conclusions: This study suggests that doses of adenosine up to 40 microg are safe and can be used to achieve a more pronounced vasodilatation in individual patients compared to the standard doses. This may have therapeutic impact with FFR values near cut-off points in patients undergoing diagnostic coronary angiography as well as in patients in whom FFR is used to assess the outcome of interventions.

Restenosis is the limiting entity after percutaneous coronary angioplasty. Vascular brachytherapy for the treatment of in-stent restenosis has been shown to reduce the repeat restenosis rate and the incidence of major adverse events in several randomized trials. Besides the beneficial effects, brachytherapy yielded some unwanted side effects. The development of new stenoses at the edges of the target lesion treated with radiation is termed edge effect. It occurs after afterloading brachytherapy as well as after implantation of radioactive stents. It is characterized by extensive intimal hyperplasia and negative remodeling. As contributing factors the axial dose fall-off, inherent to all radioactive sources, and the application of vessel wall trauma by angioplasty have been identified. The combination of both factors, by insufficient overlap of the radiation length over the injured vessel segment, has been referred to as geographic miss. It has been shown to be associated with a very high incidence of the edge effect. Avoidance of geographic miss is strongly recommended in vascular brachytherapy procedures. Late thrombosis after vascular brachytherapy is of multifactorial origin. It comprises platelet recruitment, fibrin deposition, disturbed vasomotion, non-healing dissection and stent malapposition predisposing to turbulent blood flow. The strongest predictors for late thrombosis are premature discontinuation of antiplatelet therapy and implantation of new stents during the brachytherapy procedure. With a consequent and prolonged antiplatelet therapy, the incidence of late thrombosis has been reduced to placebo levels. Edge effect and late thrombosis represent unwanted side effects of vascular brachytherapy. By means of a thorough treatment planning and prolonged antiplatelet therapy their incidences can be largely reduced. With regard to the very favorable net effect, they do not constitute relevant limitations of vascular brachytherapy.

Fractional flow reserve (FFR) as a new technique for physiological assessment of coronary stenoses could identify patients with CAD in whom the deferral of an intended PCI was more beneficial than performing the planned procedure. It is up to now unknown whether a FFR-based therapy stratification is also safe in patients with multivessel disease and complex coronary lesions. This study demonstrates in 71 symptomatic patients with predominantly multivessel disease and angiographically intermediate coronary lesions that patients do not benefit from PCI procedures in terms of overall survival, target vessel patency or clinical symptoms during 12 month follow-up if FFR is above 0.75.

A variety of different stent types is available for the treatment of coronary stenosis. However, in-stent restenosis remains the major limitation for the use of these devices. Intracoronary ultrasound (ICUS) in addition to coronary angiography provides precise measurements of coronary wall dimensions during stent implantation and of intimal hyperplasia during follow-up. The extent of coronary injury during stent implantation was shown to play an important role in neointima formation. It is characterized by endothelial exposure, intima laceration, and media permeation. Stent-induced coronary injury has been considered to depend on stent design and stent strut size with consecutive deep wall laceration. ICUS analysis showed a correlation between the stent design and the amount of neointimal tissue proliferation. The role of adventitial remodeling in the process of restenosis is discussed controversially. Post-procedural stent expansion may provoke adventitial remodeling. The stent design and stenting strategy determines the extent of peri- and post-procedural coronary injury. Post-procedural coronary morphologic changes and changes of the stent geometry depend upon the stent design. Beside further modifications as the use of drug-eluting stents the decrease of stent-related vessel injury should be an important criterion for the development of future stent design.

In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to the high incidence of recurrent restenosis. Long ISR lesions are especially prone to restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. However, VBT may be less effective in very long, diffuse ISR lesions. The present study investigated serial changes of the extent and distribution of neointima formation after beta-radiation as assessed by intravascular ultrasound (IVUS). Following interventional procedures of long ISR in 30 patients, a 40 mm or 60 mm non-centered 90Sr/90Y seed train was used for VBT. Serial (post radiation (PR) and follow-up (FU)) quantitative coronary angiography (QCA) measurements of minimal lumen diameter (MLD) and late lumen loss (LLL) and intravascular ultrasound measurements (IVUS) of cross-sectional areas of the lumen (L-CSA), stent (S-CSA) and intimal hyperplasia (IH-CSA) were performed and compared with historic controls. LLL (0.34 +/- 0.27 mm; p = 0.196), mean decrease of L-CSA (-1.0 +/- 0.8 mm2; p = 0.024) and mean increase of IH-CSA (0.5 +/- 1.3 mm2; p = 0.038) in long ISR were comparable with previously reported results of short ISR. In conclusion the average changes of lumen and intimal hyperplasia after beta-radiation of long ISR are similar to those of short ISR.

Objectives: Determination of fractional flow reserve (FFR) allows the functional assessment of coronary stenoses before and after an intervention. Preliminary data suggest that a FFR > or = 0.94 is associated with an excellent clinical outcome after stent implantation. However, these results were limited both by the number of patients included and the use of non-contemporary stent designs. We sought to determine the prognostic value of FFR measurements in a large patient cohort undergoing coronary stent implantation., Methods: Eighty-nine consecutive patients were enrolled in whom a stent implantation was performed and a pressure wire was used as a guide wire. Patients were followed for at least 6 months. Death, myocardial infarction (MI) and target vessel revascularization (TVR) were considered cardiac events. A FFR > or = 0.94 was regarded as an optimal functional result., Results: A complete follow-up was available in all patents. Pre-interventional FFR increased from 0.66 +/- 0.16 to 0.95 +/- 0.05 (p < 0.0001) after stent implantation. Sixteen (18%) events occurred during follow-up including 10 (11.2%) TVR. Final FFR was significantly higher in patients without compared to patients with an event (0.92 +/- 0.06 vs. 0.96 +/- 0.05, p < 0.003). By univariate analysis, the presence of diabetes mellitus, left ventricular function, residual diameter stenosis and final FFR were associated with a worse clinical outcome. In the multivariate analysis, only the final FFR and left ventricular function remained as significant predictors for cardiac events (relative risk, 3.50; 95% CI: 1.29-9.52, P < 0.014, and 0.97; 95% CI: 0.93-1.00, p = 0.047)., Conclusion: These results demonstrate in a nonselected patient cohort a strong correlation between FFR values after coronary stenting and subsequent cardiac events. Further studies have to investigate whether outcome after stenting might be improved by guiding the procedure with a pressure guide wire.

Following orthotopic heart transplantation (HTx), development of transplant vasculopathy (TVP) is the limiting medical entity leading to significant morbidity and mortality beyond the first year after HTx. Selection of a suitable strategy for repeat revascularisation--transcatheter angioplasty, coronary artery bypass grafting or repeat HTx--depends on various parameters including coronary morphology, left ventricular performance, comorbidity, availability of graft material and donor organs. Catheter-based interventions on the main stem of the left coronary artery are feasible, but a relatively lower primary success rate and a higher complication rate and significantly increased mortality have to be expected. We report on a patient who underwent HTx 9 years ago and developed severe transplant vasculopathy revealing significant main stem stenosis, making reintervention necessary. Due to age, coronary artery morphology and comorbidity the patient was not considered for coronary artery bypass grafting or repeat HTx. We performed successful IVUS-guided directional coronary atherectomy and stent implantation on a distal stenosis of the unprotected main stem. Our case demonstrates a predictable procedural risk and favourable primary result of left main stem angioplasty procedures, thus providing a therapeutic option for patients who are poor candidates for operative revascularisation strategies.

Coronary allograft vasculopathy (CAV) is the major factor limiting the long-term survival after cardiac transplantation. Intravascular ultrasound (IVUS) markedly improved our knowledge about in vivo morphology of CAV by precise determination of vessel morphology. In vivo studies with IVUS demonstrated that transplant vasculopathy may present with a very heterogeneous morphology suggesting a dual etiology of transplant coronary artery disease. The high incidence of donor-transmitted atherosclerosis and its role in further progression of CAV could be demonstrated by the use of IVUS. Beside intimal hyperplasia, adaptive remodeling processes of vessel and lumen geometry may have physiologic and prognostic importance. IVUS is so far the only method that allows the evaluation of compensatory enlargement and shrinkage of coronary vessels in CAV. IVUS investigations allow the assessment of CAV progression in early angiographically not visible stages. The influence of different medical treatment regimens on CAV progression can be quantified. Further studies showed that IVUS parameters may have prognostic impact on subsequent clinical events and angiographic progression of CAV. However, besides all the diagnostic information provided by IVUS, the main application of this method is currently in the field of clinical research.

Unlabelled: Stress echocardiography has been shown to be a valuable noninvasive method for the diagnosis of restenosis after coronary angioplasty. To determine the usefulness of dobutamine stress echocardiography (DSE) for assessment of restenosis after intracoronary stent implantation, we studied 50 patients (59+/-10 years; 1-vessel disease, n=16; multivessel disease, n=34) after stent implantation. After 6 month, both DSE (5-40 mcg/kg/min, 0-1mg atropine) and angiography were performed within 48 hours and evaluated in a blinded fashion. Restenosis was defined by quantitative coronary angiography as minimal lumen diameter (LD) <50% of average reference LD. Diagnostic criteria of DSE were new or worsening wall motion abnormalities in corresponding perfusion territories during stress. Angiography revealed restenosis in 8 patients; one patient had a denovostenosis distal to the stented segment (8 x left anterior descending artery, 1 ACVB to the right coronary artery). In 6 of these 9 patients, DSE was positive (mean reduction of LD 88+/-7%; sensitivity 67%), in 3 patients negative (mean reduction of LD 62+/-7%, 1 x termination of DSE because of wall motion abnormalities in an area not supplied by the stented vessel). In 38 of 41 patients without restenosis, DSE showed no stress-induced wall motion abnormalities in the LV area supplied by the stented vessel (specificity 93%)., Conclusions: DSE is a useful noninvasive method for detecting restenosis after intracoronary stent implantation. With negative DSE at follow-up, a functionally relevant stent restenosis is highly unlikely.

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.

Previous Doppler studies of transmitral flow profiles in heart transplant recipients suggested left ventricular (LV) diastolic dysfunction. The influence of left atrial filling and emptying on mitral Doppler profiles in heart transplant recipients has not been studied systematically. In the present study, pulmonary venous flow profiles, mitral flow profiles, left atrial area change and mitral annulus motion were analyzed in 20 orthotopic heart transplant recipient and 20 control subjects by transthoracic and transesophageal echocardiography and Doppler. Mitral flow profiles revealed a "restrictive" pattern with a high early-to-late diastolic flow velocity ratio in transplant patients (2.16 +/- 0.52 vs. 1.30 +/- 0.25, p < 0.0001), which was mainly due to a reduced late diastolic maximum mitral flow velocity (32.6 +/- 8.3 vs. 51.6 +/- 12.4 cm/s, p < 0.0001). Left atrial area change (35.9 +/- 13.9 vs. 58.1 +/- 17.0%, p < 0.0006) and mitral annulus motion (9.2 +/- 3.3 vs. 12.2 +/- 2.0%, p < 0.05) were reduced in transplant recipients, compared to controls. Pulmonary venous flow parameters in transplant recipients were markedly altered during systole, when pulmonary venous flow parameters are influenced primarily by atrial function rather than by diastolic LV properties: peak systolic flow velocity (45.5 +/- 8.2 vs. 62.3 +/- 14.0 cm/s, p < 0.001), maximum flow velocity ratio (0.87 +/- 0.19 vs. 1.45 +/- 0.33), time velocity integral of pulmonary venous flow during systole (9.3 +/- 2.3 vs. 17.1 +/- 4.0 cm, p < 0.001) and the systolic fraction of the time velocity integral (52.6 +/- 10.8 vs. 68.5 +/- 6.8%, p < 0.001) were lower in heart transplant recipients than in controls. These findings are compatible with atrial dysfunction and reduced mitral annulus motion. The results of this study indicate that LV diastolic dysfunction is not the only possible cause of altered transmitral Doppler profiles in heart transplant recipients. Atrial abnormalities represent a major contributing factor to altered mitral and pulmonary venous flow patterns. Analysis of transmitral Doppler profiles alone are therefore not adequate for analysis of diastolic LV function in heart transplant recipients.

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.

The pulmonary artery pressure response to exercise frequently reflects ventricular diastolic properties. The aim of this study was to determine noninvasively cardiac allograft function and pulmonary artery pressure response to stress in the early and late phases after heart transplantation (HTX). Ten patients in the early postoperative phase (3.7 +/- 1.6 months postoperatively, group I) and ten patients at least 2 years after HTX (34.3 +/- 8.3 months postoperatively, group II) were studied by two-dimensional (2 D-), M-Mode, and Doppler echocardiography during supine graded bicycle exercise (25, 50, 75, 100 watts). The patients' data were compared to those obtained in eight normal controls. The peak pressure gradient between the right ventricle and right atrium during systole was derived from saline contrast-enhanced Doppler echocardiography of the tricuspid regurgitant jet and used as an estimate of pulmonary artery systolic pressure. In group I- and group II-patients, resting and exercise left ventricular diameters as well as systolic function were normal. The right ventricle was enlarged (3.2 +/- 0.4 cm/3.0 +/- 0.6 cm in group I/group II versus 2.1 +/- 0.3 cm in normal controls, p < 0.05). During exercise, heart rate increased less in heart transplant recipients (+26%/+36% in group I/group II, p < 0.05) than in normals (+67% at 100 watts, p < 0.05). Resting pulmonary artery pressures were similar in heart transplant recipients in the early and late postoperative stage and in normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial contrast echocardiography has the potential for assessing changes in regional myocardial perfusion. We used this method to compare papaverine vasodilator response in 10 patients after orthotopic heart transplantation without acute rejection of left ventricular hypertrophy (HTX) and in 15 patients with angiographically normal coronary arteries (control group). Injections of 2 ml of sonicated iopromid (9 paired injections in HTX and 24 paired injections in the control group) were performed before and after intracoronary application of papaverine (8 or 10 mg) into the left or right coronary artery. From regional time-intensity curves, alpha (variable of curve width), area under the curve (area), peak contrast intensity (Imax) and contrast decay half-time (T1/2) were derived by from a gamma variate function. T1/2 increased from 4.2 +/- 1.2 to 7.2 +/- 4.0 s (p < 0.01) after papaverine in HTX compared to a change from 4.8 +/- 1.0 to 6.0 +/- 1.7 s (p < 0.001) in normal subjects. Alpha decreased in HTX from 0.44 +/- 0.15 to 0.27 +/- 0.10 s-1 (p < 0.01) after intracoronary papaverine injection. In the control group alpha was 0.37 +/- 0.08 s-1 at rest compared to 0.30 +/- 0.08 s-1 at hyperemic conditions (p < 0.002). Area increased in HTX from 444 +/- 261 to 910 +/- 732 U.s (p < 0.01) and in normal subjects from 352 +/- 171 to 585 +/- 262 U.s (p < 0.001). Hyperemic to baseline flow ratios for area varied from 0.9 to 3.8 (mean 2.17 +/- 1.11) in HTX compared to 1.76 +/- 0.52 (1.03 to 2.71) in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to assess left ventricular contractility in hypertensive patients with normal coronary angiography and anginal pain. An abnormally high percentage of hypertensive patients (approximately 30%) undergoing cardiac catheterization because of anginal pain and/or exercise-induced ST-segment depressions has angiographically normal coronary arteries. Possible reasons for these signs of ischemia include a microvasculopathy, metabolic abnormalities and an increased oxygen consumption as a result of left ventricular hypercontractility which was studied here. Left ventricular volumes and ejection fraction were determined in 50 patients with arterial hypertension (23 men, 27 women, age 60 +/- 8 years, RR 154 +/- 24/91 +/- 12 mm Hg) by cardiac catheterization and computerized analysis of laevocardiographies. The control group were 50 normotensives (30 men, 20 women, age 57 +/- 12 years, RR 128 +/- 12/76 +/- 8 mm Hg) without coronary artery disease. The angiographical data were correlated with age, sex. ECG, echocardiography, laboratory findings, medication and duration of hypertension. The left ventricular ejection fraction was significantly increased in the group of hypertensives (75.8 +/- 6.3 vs. 67.7 +/- 5.0%, p < 0.001). This difference was mainly due to a significantly reduced endsystolic left ventricular volume (37.1 +/- 15.3 vs. 47.7 +/- 10.8 ml, p < 0.001); enddiastolic left ventricular volume was not significantly different (140.5 +/- 26.8 vs. 149.0 +/- 27.5 ml, p > 0.1). A hyposystolic form of hypertensive heart disease was not observed in this group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac allograft vasculopathy (CAV) influences long-term survival of patients after heart transplantation. Histopathology studies have demonstrated the insensitivity of coronary angiography (CA) for detecting CAV. Intravascular ultrasound (IVUS) is an imaging technique that provides qualitative and quantitative characterization of vessel wall morphology. The purpose of this study was to compare in vivo IVUS with coronary angiography in cardiac transplant recipients and to analyze intraindividual and segmental variability of CAV involvement. IVUS studies were performed at routine follow-up angiography in 33 patients 48 +/- 23 months after heart transplantation. 134 segments (1 to 8 per patient) were classified by IVUS according to a modified Stanford score (morphometric grading from 1 to 6). Patient characteristics and laboratory findings were further compared with intimal thickening. 114/134 (85%) segments were normal with CA. In 56% of these segments, IVUS revealed mild to moderate (IVUS grade 2 to 4, n = 45) or severe (IVUS grade 5 to 6, n = 19) intimal thickening. Mean IVUS scores between proximal and distal segments were not different (2.9 +/- 1.9 vs. 2.4 +/- 1.9, ns). Intimal thickening was more pronounced in segments of the LAD compared to the RCX (3.1 +/- 2.0 vs. 2.03 +/- 1.6, p < 0.01). In 39% of patients, the intraindividual extent of CAV was very heterogeneous (range: 3 to 5 IVUS grades). There was no significant correlation between IVUS and clinical or laboratory findings. IVUS is a sensitive method for the in vivo detection of CAV, while even severe intimal thickening can often not be identified by CA.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of the calcium channel blockers diltiazem on the parasympathetic nervous system were studied by using spectral analysis of heart rate variability, and were compared with the effects of the beta-receptor blocker metoprolol. The area under the curve of the high-frequency range (f = 0.18-0.35 Hz) during controlled respiratory rate (f = 0.25 Hz) was used as a quantitative index of parasympathetic activity. Twenty-four male patients with proven coronary artery disease and normal left ventricular function (LVEF > 60%) were studied 2 weeks after chronic treatment with diltiazem (3 x 60 mg daily) or metoprolol (3 x 50 mg daily) before and after administration of the drug. Twelve patients received diltiazem and 12 patients metoprolol. After administration of diltiazem the peripheral systolic blood pressure was reduced, but the parasympathetic activity was significantly higher than compared with the initial measurement. The same effect was seen for metoprolol, but a significant lower heart rate was present after administration. The relative area under the high-frequency range significantly increased at rest, by 110% after diltiazem and 70% after metoprolol. Diltiazem and metoprolol enhance the vagal influence at the heart, thereby leading to an enhancement of barosensitivity and of the respiratory sinus arrhythmia. This action may contribute to the beneficial effects of both drugs in patients with coronary artery disease.

Experimental studies from our laboratory demonstrated that acute cardiac rejections (AR) are associated with an increase in myocardial echo amplitudes which correlate with the histologic severity of AR. The aim of the present study was to test whether AR-induced myocardial structural changes would also alter the spatial distribution of the myocardial echo amplitudes, assessed by echocardiographic texture analysis, and whether this method would improve the sensitivity of AR diagnosis. Echocardiographic LV long axis views were daily recorded in 12 dogs after cervical heterotopic heart transplantation (mean survival time: 16.1 days; immunosuppression: cyclosporine, azathioprine and prednisolone; AR treatment: pulsed steroids) under strictly standardized conditions and digitized into a 256 x 256 x 8 pixel matrix. Texture analysis using Co-occurrence- and Run Length Matrix was performed in 45 x 12 pixel-sized regions of interest (ROI) within the septum (VS) and posterior wall (PW) in end-diastole. Results obtained without AR were then compared with those during biopsy-proven mild, moderate and severe AR. Severe AR are associated with a significant increase in Co-occurrence Matrix parameters within the septum and posterior wall (Contrast: VS: 3.1 +/- 0.7 vs. 3.9 +/- 1.1, p < 0.05. PW: 1.8 +/- 0.5 vs. 2.3 +/- 1.0, p < 0.05. Variance: VS: 19 +/- 15 vs. 36 +/- 18, p < 0.05. PW: 11 +/- 6 vs. 21 +/- 8, p < 0.01). During mild and moderate AR no significant changes in texture measurements were found. Testing the influence of ROI placement on myocardial echo amplitude, texture measurements showed a high variability in comparison to mean gray level (up to 30% vs. < 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

In order to determine whether changes in myocardial perfusion can be assessed by myocardial contrast echocardiography, intracoronary injections of 2 ml of sonicated iopromid were performed before and 30 to 45 s after application of papaverine in 31 patients (mean age 58 years). 13 patients showed coronary artery disease (KHE), 6 patients hypertensive heart disease (HHE), and 12 patients had no proven heart disease (KTR). Contrast decay-halftime (T/2), maximal video-intensity (Imax) and area under the curve (Area) were derived by computer-assisted videodensitometry. After papaverine KTR showed a significant increase of T/2 (from 5.1 +/- 1.5 to 6.8 +/- 3.2 s, p < 0.05), of Imax (from 36 +/- 13 to 52 +/- 16 E, p < 0.002) and of Area (from 203 +/- 95 to 379 +/- 188 E*s, p < 0.002) compared to baseline values. In this group the ratios of hyperemia to baseline flow conditions were 1.5 +/- 0.4 (from 1.0 to 2.4) for Imax and 1.9 +/- 0.9 (from 1.1 to 3.9) for Area. In HHE and KHE, hyperemia induced no significant changes of T/2, Imax and Area. Heart rate was increased by 4.3% and mean aortic pressure was decreased by 6.2% in all groups after papaverine. Double-product was not altered significantly in any group. Myocardial contrast echocardiography revealed a significant increase in variables of contrast wash-out curves only in patients without proven heart disease. In contrast, no relevant changes of T/2, Imax and Area on average were observed in patients with coronary and hypertensive heart disease. Thus, myocardial contrast echocardiography seems to be suitable to document a reduced papaverine vasodilator response in these patients.

Clinical application of echocardiographic tissue characterization necessitates measurements through the chest wall. Different distances between transducer and myocardial region of interest result in variable attenuation effects. Therefore, meaningful comparisons of myocardial echo intensity measurements are difficult with current equipment. The present study aims at the quantification and compensation of depth-dependent attenuation effects. Ten normals, 14 patients with mild (n = 7) or moderate (n = 7) hypertensive left ventricular hypertrophy and 10 transplant candidates were examined. Gain-independent logarithmically amplified, demodulated radiofrequency signals of parasternal long axis cross-sections were digitized. Mean myocardial echo intensities were determined in septal and posterior wall regions of interest. The slope of attenuation was determined from these clinically obtained data by plotting the distances between transducer and regions of interest against myocardial echo intensities. An attenuation coefficient derived from this slope was used for compensation of the depth-dependent losses of myocardial echo intensity. Compared with normals, compensated mean myocardial echo intensities were significantly lower in mild or moderate hypertensive left ventricular hypertrophy, but showed no significant difference in transplant candidates. Despite several limitations, the method employed in this study appears to be a possible approach to in vivo quantification and compensation of attenuation.

Orthotopic heart transplantation results in altered atrial anatomy and denervation of the donor heart. To assess the impact of these sequelae on left ventricular filling and systolic performance, 16 heart transplant recipients and 10 normal controls were evaluated by Doppler echocardiography at rest and during graded bicycle exercise. Global and regional systolic ventricular allograft function was normal at rest and during exercise. Resting Doppler profiles demonstrated diminished atrial contribution to ventricular filling in transplant recipients. The response to dynamic exercise was different in both groups; controls increased heart rate, while mitral time-velocity integral was unchanged. Heart transplant recipients, in contrast, showed a blunted heart rate response and increased time-velocity integral. Atrial contribution to ventricular filling was not augmented during exercise as in normal controls. Alterations in transmitral flow profiles in heart transplant recipients do not necessarily reflect ventricular myocardial damage, but may be related to impaired atrial function.

This study was designed to evaluate quality of life and life changes after heart transplantation in long-term survivors, to compare the patients' results with those obtained from healthy subjects of similar age, and to correlate quality of life with psychological and clinical variables. Questionnaires were mailed to all 43 adult German-speaking transplant patients operated between 1982 and 1986. Forty-one (95%) of this patient population completed the questionnaires; 52 controls answered those questions not addressing transplant-specific issues. 83% of the transplant patients versus 88% of the controls rated global quality of life as "good" or "excellent". Psychological affect and well-being were comparable in both groups. 70% of the transplant patients versus only 30% of the controls stated "to be bothered by symptoms". Despite that response, heart transplant recipients perceived postoperative life changes mostly as positive, although sexual function and professional situation had worsened in 34% and 41%, respectively. Global quality of life correlated best with job satisfaction (r = 0.65, p less than 0.01), satisfaction about health (r = 0.64, p less than 0.01), well being (r = 0.53, p less than 0.01), and everyday life function (r = 0.53, p less than 0.01), and correlated negatively with depression (r = -0.40) and physical symptoms (r = -0.36). The study shows that the subjective quality of life of long-term survivors after heart transplantation is similar to that of healthy individuals of the same age group. Thus, survival is certainly not the only indicator of success; aspects of quality of life must also be included in cost effectiveness and/or cost benefit considerations in transplantation policies.

In 15 patients with essential hypertension (but without coronary heart disease) simultaneous 24-h monitoring of the ST-segment and blood pressure was performed. Twenty-six periods with significant ST-segment depressions were recorded. In 10/26 periods with ST-segment depressions blood pressure was elevated, heart rate was increased in 20/26 ST-segment depressions. During nine periods with ST-segment depressions angina pectoris was reported, and 27 anginal attacks without ST-segment depressions were observed. These data show ischemic episodes in hypertensive patients without coronary heart disease being associated with spontaneous increases of blood pressure and/or heart rate.

We studied the effect of barucainide, an investigational class lb antiarrhythmic drug, on ventricular arrhythmias and left-ventricular ejection fraction in 10 patients with frequent and complex ventricular arrhythmias (Lown grade 4a/4b). The study was conducted as a single-blind and placebo-controlled trial. With placebo, mean frequency of ventricular arrhythmias was 6238 VPB/24 h, 510 couplets/24 h, and 24 salvos/24 h. Mean left-ventricular ejection fraction was 37.6%, ranging from 18% to 58%. Therapy with barucainide (300-400 mg/day) resulted in a significant reduction of ventricular arrhythmias in 7 of 10 patients; in one patient barucainide had a clear proarrhythmic effect. Over all, left-ventricular ejection fraction (37.6% +/- 12% with placebo vs 36.1% +/- 11% with barucainide) was not significantly altered. In one patient, however, it was depressed by more than 5%; one patient complained of shortness of breath during exercise. None of the four patients with an initial ejection fraction below 35% showed a drop of ejection fraction during therapy with barucainide. The only main adverse effect was a small, but significant (p less than 0.005) rise of serum-kreatinine (1.13 +/- 0.26 vs 1.39 +/- 0.38 mg%) in all patients. We conclude that barucainide has a good antiarrhythmic effect and is usually well tolerated in patients with markedly depressed left-ventricular function. The mechanism causing the rise of serum-kreatinin, however, needs to be clarified in further studies.

The aim of this prospective study was to investigate both vasoconstricting and vasodilating plasma hormones and plasma factors regulating the circulatory homeostasis in patients with endstage congestive heart failure before and early after orthotopic heart transplantation and to evaluate factors which may influence their regulation. 19 patients with endstage congestive heart failure were analyzed serially before and 3-4 weeks after orthotopic heart transplantation. A significant decrease in plasma concentrations of noradrenaline (457 +/- 202 vs. 204 +/- 88 pg/ml; p less than 0.001), adrenaline (43 +/- 32 vs. 26 +/- 11 pg/ml), atrial natriuretic peptide (341 +/- 218 vs. 139 +/- 64 pg/ml; p less than 0.005), cyclic guanosine monophosphate (13.8 +/- 7.8 vs. 6.6 +/- 2.2 pmol/ml, p less than 0.05) and in plasma renin activity (16.6 +/- 13.0 vs. 2.0 +/- 2.4 ng AI/ml/h; p less than 0.01) was found after transplantation. The data indicate that the marked increase in plasma catecholamine concentrations and renin activity in endstage congestive heart failure is reversible as early as 3-4 weeks after heart transplantation. This is most likely the consequence of normalization of cardiac function. While elevation of atrial natriuretic peptide and cyclic guanosine monophosphate as well as increased vasoconstrictor activity in heart failure appear to be related to impaired ventricular function, the persistent moderate elevation of both vasodilating agents after transplantation may be compensatory to counteract cyclosporin-induced arterial hypertension after heart transplantation.

Thirty-one patients (3 female, 28 male, mean age 56 years) were investigated with myocardial contrast echocardiography before and after successful PTCA (= less than 30% residual stenosis) of one major coronary artery. 2 ml of sonicated lopromid (Ultravist 370, microbubble-size 6 +/- 4 microns) were injected into the coronary vessel. Before, during and after injection a short-axis view or an apical four chamber view was obtained and recorded on videotape. Computer-assisted videodensitometry was performed in a region of interest placed between endo- and epicardium of the myocardial area supplied by the dilated vessel to analyze contrast decay half-time (t/2), time from onset of opacification to t/2 (T-t/2) and maximal videointensity (Imax). 27 patients (87%) had adequate echorecordings before and after PTCA, no side-effects occurred. Contrast decay half-time and T-t/2 showed a decrease in 21/27 (78%) patients (8.7 +/- 6.1 vs 5.8 +/- 3.7s, p less than 0.001) and in 19/27 (70%) patients (12.0 +/- 8.4 vs 8.7 +/- 5.0 s, p less than 0.002) respectively. Imax was not significantly altered by the intervention. Most of the patients without decrease of t/2 and T-t/2 either had moderate coronary stenosis or a preexisting myocardial infarction in the region supplied by the dilated vessel. Thus contrast echocardiography seems to be suitable to assess alterations in myocardial blood flow during PTCA by determination of contrast decay half-time and T-t/2.

In order to minimize the rate of inadequate myocardial revascularizations, an intraoperative evaluation of regional myocardial perfusion could have practical impact. Current bypass flow measurements have inherent limitations and can determine only epicardial blood flow. To analyze regional graft-dependent myocardial blood flow an echocardiographic short-axis view of the left ventricle was performed intraoperatively in 11 patients undergoing elective coronary artery bypass surgery. After injection of 2 ml of sonicated lopromid (Ultravist 370) into 14 vein grafts, contrast enhancement in the corresponding myocardial regions was clearly visible, no side-effects occurred. Contrast decay halftimes (T/2) were determined by computer-assisted videodensitometry and compared to electromagnetic flow (EMF) rates, which were measured immediately before. T/2 ranged from 2.1 to 6.9 (mean 4.1 +/- 1.5) s and did not correlate to the EMF-rates of 55 to 100 (mean 80 +/- 16) ml/min. Thus intraoperative myocardial echocardiography is a safe and feasible method which allows on-line visualization and off-line quantitation of regional myocardial perfusion intraoperatively.

In 15 patients with essential hypertension, anginal pain, and angiographically excluded coronary artery disease 24-h monitoring of the ST-segment and blood pressure was performed. 26 episodes with ST-segment depressions 0400.1 mV were recorded in 11/15 patients. In 10/26 episodes with ST-segment depressions blood pressure was elevated above 150/95 mm Hg or by more than 20% as compared to three successive measurements before the ST-segment depressions. Heart rate was increased by more than 20% in 20/26 ST-segment depressions. During 9 periods with ST-segment depressions angina pectoris was reported; in addition 27 anginal attacks without ST-segment depressions were observed. A significant, positive correlation between the diastolic (p less than 0.005) and systolic (p less than 0.02) blood pressure and the extent of the ST-segment depression was observed. These correlations imply a patho-physiological meaning of ST-segment depressions in hypertensive patients.

In the present study, we took whole blood from 12 patients treated with heparin, acetylsalicylic acid, and nitroglycerin i.v., to measure the aggregability of platelets after acute and prolonged i.v. application of nitroglycerin and after oral application of molsidomine. Aggregation was induced by platelet-activating-factor (PAF). As a measure for platelet aggregability, we determined the PAF-concentration needed to induce irreversible aggregation (threshold dose) and the maximum slope of the aggregation curve with 50 nM PAF. At the beginning, 1 h after the onset of nitroglycerin infusion (3 mg/h), 24 h and 1 h after increasing the nitroglycerin dose (5 mg/h), neither the maximum slope nor the threshold dose for PAF-induced aggregation differed significantly. However, after additional oral application of molsidomine the maximum slope of the aggregation curve decreased significantly. These data indicate that molsidomine decreases the aggregability of platelets in patients, even after pretreatment with heparin, acetylsalicylic acid, and nitroglycerin.

Ibopamine (IP) is a novel dopamine analogue for which beneficial effects have been shown in chronic heart failure. Hemodynamic effects of the substance include an increase in cardiac output and a decrease in the peripheral resistance. Aside from these hemodynamic effects, changes in renal (increased diuresis) and neurohumoral parameters (decreased plasma renin activity, aldosterone, norepinephrine, increased ANF and cGMP) have been found. The renal effects may originate from three independent mechanisms: 1) direct impact of improved hemodynamic parameters on the renal perfusion; 2) the improved cardiac performance results in a reduction of compensatory hormonal adaptations, such as the activation of the renin-angiotensin-aldosterone-axis or the sympathetic system; 3) direct effects on the intrarenal hemodynamic and glomerular/tubular functions induced by stimulation of renal dopaminergic receptors. The continued decrease of the plasma renin activity by 35% results in a reduction of the plasma levels of angiotensin II and aldosterone. Additionally, an increase in plasma atrial natriuretic factor (ANF) and its second messenger cyclic guanosine monophosphate (cGMP) was observed after ibopamine, which could contribute to the diuretic action of the drug. These findings underline the importance of extrarenal effects of a drug in the treatment of heart failure, this may essentially contribute to the improvement of cardiac performance, independent of positive inotropy.

Ibopamine is a novel oral dopamine analogue with positive inotropy and diuretic effects. In a double-blind, randomized study, the drug was investigated in 10 patients (mean age 49 +/- 10 years, six male, four female) with mild heart failure (NYHA classes II: six patients, III: four patients). Effects of single oral doses of 200 mg ibopamine, of 40 mg furosemide, and of 200 mg ibopamine plus 40 mg furosemide were compared in each patient at 3-day-intervals. One h after application, systolic and diastolic blood pressure increased from 119 +/- 11 to 124 +/- 8, and from 75 +/- 4 to 80 +/- 6 mm Hg (p less than 0.01) in the ibopamine group, while changes in both other groups and changes of the heart rate were insignificant. During 2 h after drug ingestion urinary flow was raised from 124 +/- 81 to 227 +/- 166 ml/2 h in the ibopamine group (p less than 0.05), while the application of furosemide (with or without ibopamine) resulted in several fold increases of urinary flow. After ibopamine, the 2-h-creatinine-clearance rose from 123 +/- 73 to 130 +/- 85 ml/min (not significant). Sodium excretion remained unchanged by ibopamine, potassium excretion was increased from 2.9 +/- 1.7 to 4.0 +/- 3.3 mmol/h (p less than 0.05), while effects of furosemide were several fold of those of ibopamine. Atrial natriuretic factor concentrations in plasma increased significantly after ibopamine and after ibopamine plus furosemide (p less than 0.01), but remained constant after furosemide alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Infection remains a major problem in the early phase after heart transplantation. Immunosuppressive therapy is the most important predisposing factor. It may also reactivate preexisting latent endogenous infections. Unspecific symptoms and a chronic clinical course, as described in this report, may suggest infective endocarditis of the cardiac allograft. From this case, we do not suggest a general antibiotic prophylaxis for heart transplant recipients; however, special precaution should be considered in heart transplant patients with a history of endocarditis.

In the treatment of myocardial ischemia in hypertensive patients, nitrates as the basic compound have to be combined with another substance in order to achieve a maximum effect and a 24-h-protection. As these patients often show an impaired left ventricular function because of arterial hypertension or previous myocardial infarction, a further deterioration of the left ventricular ejection fraction (EF) has to be avoided. We therefore investigated in a pilot study. EF, blood pressure, and ST-segment depression under isosorbide dinitrate 120 mg s.r. alone, and in combination with verapamil 120 mg s.r. in 14 male patients with angiographically proven coronary artery disease and arterial hypertension. EF at rest ranged from 29% to 76%. Radionuclide ventriculography was performed at rest and simultaneously with the ECG during exercise before medication, 2 h after ISDN and 4 h after the additional intake of verapamil. The systolic blood pressure at rest fell from 159 +/- 14 to 132 +/- 10 (p less than 0.001) after 2 h and to 132 +/- 16 mmHg after 6 h (p less than 0.01). During exercise there was a decrease from 196 +/- 21 to 174 +/- 21 (p less than 0.01) and to 178 +/- 22 mmHg (p less than 0.001), respectively. The ST-segment depression was reduced from 2.2 +/- 1.1 to 0.8 +/- 0.6 (p less than 0.01) and to 0.9 +/- 0.5 mm (p less than 0.001). EF at rest improved from 53 +/- 14% to 57 +/- 14% after ISDN alone and to 58 +/- 15% after ISDN + verapamil (p less than 0.01), and during exercise from 57 +/- 20% to 62 +/- 19% (p less than 0.05) and to 61 +/- 17% (n.s.). Even in the subgroup of patients with impaired LV-EF (8 at rest and 7 pts during exercise) there was a significant improvement (p less than 0.05) as well after ISDN alone, as there was with combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

An endothelial injury that leads to local thrombogenicity is produced during angioplasty and persists after successful thrombolysis. Thus the risk of thrombosis is augmented after these interventions. The high grade coronary stenosis remaining after lysis increases the shear forces, again stimulating thrombus formation. A higher recurrence rate after angioplasty is seen in the presence of a wall thrombus. Therefore antithrombotic therapy is of importance not only for prophylaxis of reocclusion but also for prevention of restenosis after angioplasty. During angioplasty reduction of wall thrombus formation by acetylsalicylic acid in addition to heparin could be shown, and is likely after lysis. A low dose regimen of acetylsalicylic acid appears to be as effective as high dose treatment and minimizes adverse gastrointestinal reactions. A reduction of thrombotic occlusions of about 50% seems possible. The platelet inhibiting effects of beta blockers an Ca antagonists are not of clinical importance. There is no perfect antiplatelet agent for prophylaxis of occlusion and restenosis, so a combination of drugs with different modes of action may be necessary.