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This study prospectively compared the impact of cyclosporine A and tacrolimus on the development of cardiac allograft vasculopathy. By using serial intravascular ultrasound examinations, a trend toward a more pronounced progression was noted in the tacrolimus group in the first year after heart transplantation. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to test the hypothesis that a niobium stent might lower the restenosis rate in de novo coronary lesions as compared to a bare metal stent., Background: Recent data have suggested that inflammatory and allergic reactions to certain compounds in metal stents may play a role in the onset of restenosis. Thus, niobium as an inert material might be beneficial in lowering the rate of restenosis., Methods: In this single blind, two-center prospective trial patients were randomized into two groups; the first group (n=32) received a niobium stent (VELA STF), the second group (n=33) a bare metal stent (Antares STF). Clinical follow-up was performed at 1 and 6 months, angiographic and intravascular ultrasound analyses were performed at the 6-month follow-up., Results: All stents were successfully deployed. There was one stent thrombosis in each group. There were no significant differences concerning minimal lumen diameter, percent stenosis, and late lumen loss as assessed by intravascular ultrasound (IVUS) at the 6- month follow-up. At 30 days and at 6 months, there were no differences observed between the two groups regarding the rate of major cardiac adverse events. Immediately after stent implantation minimal lumen diameter was significantly larger (p=0.01) and residual percent stenosis significantly lower (p=0.01) in the niobium stent group., Conclusion: The use of a niobium stent showed comparable results with other non-drug-eluting stents; however the inert qualities of this first generation niobium stent did not translate into a mid- or long-term benefit.

Primarily described in Japan, tako-tsubo-like left ventricular dysfunction is a phenomenon characterized by transient apical ballooning in the absence of significant coronary artery disease. The clinical presentation includes symptoms like chest pain, dyspnea, syncope, electrocardiographic changes and elevated myocardial markers, all compatible with the diagnosis of an acute coronary syndrome. The underlying mechanism is supposed to be a catecholamine excess caused by various triggers. We describe a patient with a recurrent tako-tsubo phenomenon, who at work-up proved to have a pheochromocytoma as the most likely underlying disease.

Background and Objective: Percutaneous transluminal angioplasty and stenting of internal carotid artery stenosis has been increasingly practiced as an alternative to carotid embolectomy, particularly since the development of cerebral protection devices. 100 consecutive elective percutaneous carotid stenting procedures were carried out in our centre. We here present the clinical outcome and follow-up of these patients., Patients and Methods: 69 men and 22 women, average age 69 +/- 10 years with symptomatic (41 %) or asymptomatic and progressive (59 %) > 80 % stenosis of the internal carotid artery were treated. There was a high rate of co-morbidity and a high vascular risk. 64 % would have been excluded from the NASCET trial because of one, 31 % because of two or more contraindications. In 84 % of the patients symptomatic coronary artery disease was present, in 13 % a significantly reduced left ventricular function (LVEF < 40 %).Pre- and post-procedure all patients were given aspirin and clopidogrel and examined by an independent neurologist. 99 stents were placed with the use of an embolic protection device (28 times with distal balloon occlusion, 72 times with a filter device).The follow-up period averaged 10.4 +/- 8.2.(1 - 29 months)., Results: The angiographic success rate was 99 %. During the procedure transient neurological symptoms were experienced by 4 % of patients (2x TIA,2x PRIND) and a minor stroke resulted in two. In 90 % of the interventions debris was collected from the embolic protection device. The maximum diameter of particles was 311+/-431 (30 - 1850) micro m. There was some correlation between patients' symptoms prior to stent implantation and maximum particle size (p < 0,04),but none with any other angiographic or clinical parameters. The combined endpoint (death and any stroke) after 30 days occurred 5 times (5 %). A subacute stent thrombosis occurred once, restenosis in two patients., Conclusion: Carotid artery stenting with use of a distal embolic protection device is a feasible new alternative to carotid endarterectomy. Our results indicate high success rate and low complication rates, even in patients with severe co-morbidity. The results compare well with surgical figures. Our favourable results are supported by data emerging from current randomized multicenter trials and a large therapy registry. However, long-term follow-up will still be required.

Intravascular sonotherapy has been introduced as a potential alternative to brachytherapy for prophylactic and therapeutic application in patients after coronary stent placement. Sonotherapy represents a non-ablative, non-thermal form of therapeutic ultrasound. The ultrasound catheter with diameter between 4 and 5 French carries up to 6 electronic elements operating currently at a frequency of 1.0 to 1.4 MHz. Animal studies have proven the efficacy of intravascular sonotherapy with respect to a reduction of neointimal ingrowth after stent placement. A first multicenter observational study in humans has documented that its application is safe and yields favorable results after coronary stenting, also in complex patient and lesion characteristics. This technique is currently under investigation in large prospective, multicenter, randomized studies performed in patients with de novo stenting or documented in-stent restenosis.

Invasive methods as coronary angiography and intravascular ultrasound (IVUS) are still the routine tools for diagnosis of cardiac allograft vasculopathy (CAV). Nevertheless, invasive tests are expensive and not free of risk. Dobutamine stress echocardiography (DSE) emerged as a useful noninvasive tool for assessment of cardiac allograft vasculopathy (CAV). In our study, echocardiographic wall motion abnormalities (WMA) at rest had a sensitivity of 57% (specificity 88%) to detect CAV defined by IVUS and angiography, which was significantly (p < 0.0001) improved to 72% (specificity 88%) by stress testing. Additional M-mode analysis of systolic wall thickening improved the sensitivity of the resting echocardiogram to 72% (specificity 85%), the combined M-mode and 2D-analysis during stress had a sensitivity of 85% (p < 0.0001; specificity 82%). DSE was also useful to predict prognosis: 1.9% of patients with normal, but 27.3% of patients with abnormal 2D-DSE developed cardiac events (heart failure, infarction, death, re-HTX, PTCA) between annual studies (p < 0.0002). No change in serial DSE studies was associated with a low event rate (4%), compared to serial DSE deterioration (29%, p < 0.0014). Based on our experience, we postpone invasive studies for 12-24 months, if DSE is normal or remains unchanged in serial studies. Angiography is used in patients with abnormal or deteriorating DSE. In conclusion, noninvasive DSE provides useful diagnostic and prognostic information. It appears safe to use DSE as a first step of CAV monitoring.

Background: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography., Methods: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR., Results: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR., Conclusion: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.

Background: There are no well-established diagnostic criteria to detect humoral rejection in organ transplantation. The value of commonly used markers in immunohistochemistry, such as C1q, C3c, IgG, IgM and fibrinogen, is questioned by some groups. Complement fragment C4d is a more stable marker of complement activation as it is covalently bound to graft capillaries. C4d has been shown to identify clinically relevant, but otherwise undetectable humoral anti-graft reactions in human kidney transplants., Methods: Immunohistochemical techniques were used to evaluate 155 endomyocardial biopsies from 56 heart transplant recipients less than 3 months post transplantation for the presence of capillary C4d staining. In a subset of patients, C4d staining was compared with C1q, C3c, IgM and fibrin staining and was correlated with clinical outcome., Results: Within 3 months 9 of 56 patients died. Five of these nonsurvivors had prominent C4d staining (p < .05), whereas C1q, C3c and IgM showed no correlation with clinical outcome. Presence of fibrin correlated with clinical outcome and C4d staining (p < .05)., Conclusions: The capillary deposition of complement split product C4d in human endomyocardial biopsies was significantly associated with graft loss. Determination of fibrin deposition may yield additional information to establish a diagnosis of humoral rejection. The immunohistochemical assessment of capillary deposition of C4d and fibrin appears to be an appropriate tool for the identification of patients, who may require additional or alternative immunosuppressive therapy targeted against the humoral immune system.

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.

Rapid nongenomic in vitro effects of aldosterone have been demonstrated recently in cultured vascular smooth muscle and endothelial cells. But there is, as yet, little evidence for corresponding in vivo effects. The present study thus investigates the rapid nongenomic effects of aldosterone on human cardiovascular function. In a double-blind placebo-controlled randomized parallel trial on 17 patients with suspected coronary heart disease, the effect of 1 mg aldosterone iv on cardiovascular function was assessed during cardiac catheterization. Hemodynamic parameters (such as heart rate, left ventricular and atrial pressures, arterial pressures, vascular resistances, and cardiac output) were measured before and 3 and 10 min after administration of aldosterone or placebo. Significant changes were found for systemic vascular resistance, cardiac output, and cardiac index, compared with the placebo group (Wilcoxon test, P < 0.02-0.05). The effect of aldosterone dissipated within 10 min. The results are in line with the in vitro data cited above and consistent with earlier findings on acute cardiovascular effects of aldosterone, which have now been confirmed and extended by contemporary techniques. The hypotheses of rapid nongenomic in vivo effects of aldosterone are further substantiated by this study.

Background: The aim of this study was to investigate whether adult human cardiomyocytes may reexpress vimentin and whether this is linked to cellular activation., Methods: Myocardial samples of 81 heart transplant recipients (n=183) and patients with dilated cardiomyopathy (n=10) were investigated by immunohistochemistry with the use of the marker molecule vimentin, the muscle-specific protein desmin, and Ki67, a marker for cell activation., Results: Vimentin protein expression in cardiomyocytes was found in 28 samples of transplant recipients and 5 myocardial samples of patients with dilated cardiomyopathy. Coexpression of vimentin and Ki67 was found in 52 of 340 vimentin-positive cardiomyocytes., Conclusions: We suggest that the vimentin/Ki67 coexpression indicates cell activation processes as the result of different growth stimuli.