[Coronary restenosis]. / Koronare Restenose.

Coronary restenosis is the answer of the arterial wall to a mechanical violation through balloon angioplasty, bare-metal (BM) stent implantation or rotational atherectomy through repeated narrowing. It has great clinical and prognostic relevance and occurs in approximately 30% of non-coated stents and in 10% of coated coronary stents. The wound healing process that precedes restenosis includes inflammatory reactions, cellular proliferation and remodeling of the arterial wall, where protein synthesis of the extracellular matrix is initiated. The inflammatory reaction activates platelets, leucocytes and monocytes and stimulates smooth muscle cells. The medications on the drug-eluting stents (rapamycin, paclitaxel, sirolimus, evarolimus and zotarolimus) inhibit cell division, are cytotoxic and only these sustainably influence restenosis. Whether they play a role in neoatherosclerosis needs to be determined. The mechanism of restenosis with implantation of drug-eluting stents is heterogeneous and associated with the deposition of T­lymphocytes and fibrin. Risk factors for the development of restenosis include mechanical factors, such as incorrect apposition and expansion of stents, inflammation, diabetes mellitus, genetic factors, bypass operations, stent length and stent diameter. The restenosis rate is lower with drug-eluting stents and must be considered differently between the drug-eluting stents. Drug-eluting stents of the latest generation and drug-coated balloons (DCB) showed the best clinical and angiographic results for in-stent restenosis in randomized trials. The BM and older first-generation drug-eluting stents should be avoided. Further randomized studies are needed.

Guideline-adherent therapy in patients with acute coronary syndromes. The EPICOR registry in Germany.

BACKGROUND: Representative data on the current management of patients with acute coronary syndromes (ACS) are of high interest. The EPICOR registry aimed to prospectively collect such real-life data with particular focus on antithrombotic drug utilization and outcomes. METHODS: As part of the international prospective EPICOR registry, 29 hospitals in Germany documented 296 patients with ST-elevation myocardial infarction (STEMI)-ACS and 333 with unstable angina or non-STEMI (NSTEMI)-ACS surviving the hospital phase. The statistical analysis was performed in a descriptive manner. The ClinicalTrials.gov identifier is NCT01171404. RESULTS: The mean age of patients was 62 ± 13 years, and 77.4 % were men. Treatment with antithrombotic agents was initiated in the prehospital phase in 50.7 % of STEMI and 33.3 % of NSTEMI patients. During the hospital stay (median 7.0 days), cardiac catheterization was performed in 97.6 %, percutaneous coronary intervention in 85.6 %, thrombolysis in 4.6 %, and coronary bypass surgery in 2.7 % patients. The use of acetylic salicylic acid (ASA) was reported in 95.6 % vs. 96.1 %, clopidogrel in 60.8 % vs. 73.0 %, prasugrel in 45.6 % vs. 22.5 %, any GP IIb/IIIa inhibitor in 52.4 % vs. 18.9 % [any dual combination of ASA+(clopidogrel/prasugrel)in 94.0 vs. 91.0 %], statins in 94.6 % vs. 92.2 %, beta blockers in 96.3 % vs. 94.6 %, and ACE-I/ARB in 91.6 % vs. 87.7 % of STEMI vs. NSTEMI patients, respectively. Combined use of the five drug classes recommended in the guidelines-ASA, P2Y12 antagonists, statin, beta blocker, and ACE-I/ARB-was reported in 81.1 % vs. 69.4 % of STEMI vs. NSTEMI patients, respectively. CONCLUSION: In Germany a high proportion of patients with ACS are treated according to current guidelines, receiving primary revascularization as well as antithrombotic drugs and other agents for prevention of secondary events; associated bleeding complications were less frequent as compared with published registries.

[The length of hospital stay in patients with acute coronary syndrome is reduced by establishing a chest pain unit]. / Reduktion der stationären Verweildauer bei Patienten mit akutem Koronarsyndrom durch Einrichtung einer Chest Pain Unit.

BACKGROUND: Providing prompt and appropriate therapy, combined with the increased economic requirements of treating patients with acute coronary syndrome (ACS), places high demands on the emergency department. The aim of the present analysis is to evaluate to what extent establishing a dedicated chest pain unit (CPU) influences the length of hospital stay in ACS patients. METHODS: Patients presenting with suspected ACS between 05/2004 and 05/2006 to either the emergency department (ED) or the newly established CPU were retrospectively analyzed. The CPU became functional in July 2005. Data were obtained according to standardized procedures based on patient charts and all available clinical information. RESULTS: A total of 247 patients were treated in the ED and 765 in the CPU. In the ED patient group 29 (11.7%) were diagnosed with ST elevation myocardial infarction (STEMI), 38 (15.4%) with non-ST elevation myocardial infarction (NSTEMI) and 15 (6.1%) with unstable angina pectoris (UAP), while ACS could be excluded in 165 (66.8%) patients. Patients treated in the CPU showed a higher percentage of ACS with 75 (9.8%) STEMI, 128 (16.7%) NSTEMI and 136 (17.8%) UAP patients; ACS could be excluded in 426 (55.7%) patients. The median length of hospital stay was shorter in ACS patients treated in the CPU at 5.0 days compared to 8.0 days if admitted to the ED (p<0.001). No difference in length of hospital stay was observed in UAP patients, whereas in STEMI patients admitted to the ED the time was longer at 8.0 days compared to 7.0 days if admitted to the CPU (p=0.042). A reduction from 8.0 to 6.0 days in the length of hospital stay if admitted to the CPU compared to the ED could be observed (p=0.002) in NSTEMI patients. CONCLUSIONS: Establishing a chest pain unit with optimized diagnostic and structural processes is associated with reduced lengths of hospital stay in patients with ACS treated according to current guidelines and recommendations.

Argatroban for elective percutaneous coronary intervention: the ARG-E04 multi-center study.

UNLABELLED: The synthetic arginine-derived direct thrombin inhibitor argatroban is an attractive anticoagulant for percutaneous coronary intervention (PCI), because of its rapid onset and offset, and its hepatic elimination. Argatroban was approved for PCI in patients with heparin-induced thrombocytopenia (HIT). However, there are limited data about argatroban in non-HIT patients. The objective of this open-label, multiple-dose, controlled study was to examine the safety and efficacy of argatroban in patients undergoing elective PCI. METHODS AND RESULTS: Of 140 patients randomized to three argatroban dose groups (ARG250, ARG300, and ARG350 with 250, 300, or 350 µg/kg bolus, followed by 15, 20, or 25 µg/kg/min infusion) and one unfractionated heparin (UFH) group (70-100 IU/kg bolus), 138 patients were analyzed. Argatroban dose-dependently prolonged activated clotting time (ACT) with more patients reaching the minimum target ACT after the initial bolus injection (ARG250: 86.1%, ARG300: 89.5%, and ARG350: 96.8%) compared to 45.5% in UFH (p<0.001). The patient proportion who did not require additional bolus injections to start PCI was significantly higher in argatroban than in UFH (p ≤ 0.002). Consequently, the time to start of PCI was shortened in argatroban groups. Composite incidences of death, myocardial infarction, and urgent revascularization until day 30 were not significantly different between the groups (ARG250: 2.8%, ARG300: 0.0%, ARG350: 3.2% vs. UFH: 3.0%). Major bleeding was observed only in UFH (3.0%), while minor bleeding occurred in ARG350 (3.2%) and UFH (6.1%, n.s.). CONCLUSION: Argatroban dose-dependently increases coagulation parameters and, compared to UFH, demonstrates a superior predictable anticoagulant effect in patients undergoing elective PCI.

Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeutic effect of allopurinol.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide-dependent vasodilation. In 113 patients with chronic heart failure (CHF) and 26 controls, ADMA level was studied in relation to peripheral blood flow and vasodilator capacity. Further, the effects of allopurinol on concentrations of reactive oxygen species (ROS) and ADMA and peripheral vasodilator capacity were tested in a double-blind design. ADMA level was found to be elevated in CHF patients as compared with controls and increased in parallel with New York Heart Association (NYHA) class and exercise capacity (all P < 0.0001). The level of ADMA predicted resting blood flow (P < 0.05) and postischemic vasodilator capacity (P < 0.001). Sixty eight patients died during the follow-up period. The level of ADMA predicted survival after multivariable adjustment (P = 0.04). Allopurinol reduced uric acid (UA) concentration (P < 0.001) and decreased ROS concentration (allantoin, P < 0.01). Allopurinol lowered ADMA concentration (P = 0.02); postischemic vasodilation as well as endothelium-dependent vasodilation (both P < 0.05) improved. ADMA may be a pathophysiologic factor that is modulated by ROS accumulation and contributes to impaired vascular regulation in CHF.

[Patient satisfaction in acute coronary syndrome. Improvement through the establishment of a chest pain unit]. / Patientenzufriedenheit beim akuten Koronarsyndrom. Verbesserung durch die Etablierung einer Chest-Pain-Unit.

BACKGROUND AND PURPOSE: Chest pain units (CPUs) were established primarily in the United States with the aim of reducing hospital admissions and costs, whilst improving quality of life and patient care. Clinical trials have shown that these units are safe and practical; however, there was a need to investigate to what extent patients are satisfied with the care in CPUs. The aim of this study is to evaluate the experiences of patients receiving CPU care and routine emergency department (ED) treatment for acute chest pain. PATIENTS AND METHODS: Patients presenting with acute chest pain at the ED between May 2004 and June 2005 and at the CPU between July 2005 and May 2006 were evaluated in this retrospective analysis. Standardized data collection using all available clinical data as well as telephone follow-up was carried out. Evaluation was carried out on a school-mark basis and a quality assessment was performed. RESULTS: Of the total population, 479 patients (323 male, 156 female) were treated in the ED, whereas 1176 (743 male, 433 female) in the CPU. In the ED, 26 patients (5.4%) were diagnosed as ST segment elevation myocardial infarction (STEMI), 39 (8.1%) as non-ST segment elevation myocardial infarction (NSTEMI) and 16 (3.3%) as unstable angina pectoris (UAP). In 398 patients (83.1%) acute coronary syndrome (ACS) could be ruled out. In the CPU, the incidence of STEMI was 74 (6.3%), of NSTEMI 141 (12%) and of UAP 153 (13%). ACS was excluded in 808 patients (68.7%). Data on satisfaction with in-hospital treatment was available in 78.5% of cases. In the CPU, 92.2% of the patients judged their treatment as excellent/good, 5.9% as appropriate and 1.9% as poor. The distribution of satisfaction in the ED was significantly lower with 78.6% excellent/good, 18.5% appropriate and 2.9% poor. CONCLUSION: The establishment of a CPU at the University Medical Center of Mainz demonstrated a higher level of patient satisfaction compared to the treatment of patients with acute chest pain in the general ED.

[Acute coronary syndrome (without ST-elevation)]. / Das akute Koronarsyndrom (ohne ST-Hebung).

Antithrombotic therapy in acute coronary syndrome without ST-segment elevation should be initiated with aspirin 100 mg/day (loading dose 250-500 mg) and Clopidogrel 75 mg/day (loading dose 300 mg). In addition, anticoagulation with unfractionated heparin or low molecular weight heparin should be started. A GP IIb/IIIa receptor blocker can be given either upfront (Eptifibatide/Tirofiban) or directly in the cathlab preceding PCI (Abciximab). Aspirin should be given in the chronic phase lifelong, Clopidogrel for at least nine months. An invasive strategy is recommended in high-risk patients within 48 hours.

[Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease. The AtheroGene case control study]. / Einfluss genetischer Variationen des Cholesterylestertransferproteingens auf die Prävalenz der koronaren Herzerkrankung. Athero Gene Fallkontrollstudie.

BACKGROUND: Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD. METHODS AND RESULTS: In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore. CONCLUSION: CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.

[Immunactivation in chronic heart failure. Inflammatory mediators]. / Immunaktivierung bei chronischer Herzinsuffizienz. Inflammatorische Mediatoren.

Inflammatory cytokines are thought to contribute to the development and progression of chronic heart failure (CHF). It has been shown that especially tumor necrosis factor-alpha (TNF) is activated in patients with CHF and exerts detrimental effects on the myocardium. Recent studies have demonstrated that circulating levels of TNF, soluble TNF receptors 1 and 2 and interleukin-6 are strong prognostic markers. The results of two randomized studies directly antagonizing TNF in CHF patients were rather disappointing. Nevertheless, TNF antagonism remains a therapeutic option and should be focussed on patients with systemic immune activation, particularly at times of exacerbation.

Cachexia: a therapeutic approach beyond cytokine antagonism.

Cachexia is seen in a number of chronic diseases, and it is always associated with a poor prognosis. Irrespective of etiology, the development of cachexia appears to share a common pathophysiological pathway. This includes induction of proteasome-dependent myofibril-degradation, which is thought to be secondary to stimulation by enhanced levels of pro-inflammatory cytokines. Elevation of tumor necrosis factor-alpha (TNFalpha) and other plasma cytokines has been demonstrated in many conditions associated with cachexia. Despite improved pathophysiological understanding, a specific treatment for cachexia has not yet been established. Whilst direct TNFalpha antagonism has therapeutic appeal, this review will focus on manipulation of downstream pathways and the potential benefits. For example, nuclear factor-kappaB (NF-kappaB) is one of the most important signal transducers of TNFalpha, and drugs targeting this signalling cascade might be useful in the treatment of cachexia. Although the use of some of these substances, for example glucocorticoids, remains controversial, others may prove beneficial in the treatment of this syndrome. The role of other approaches such as proteasome-inhibitors remains to be elucidated. Alternatively, interleukin-10 and other immunosuppressive cytokines may also be able to counterbalance certain features of cachexia.

Spontaneous echo contrast caused by platelet and leukocyte aggregates?

BACKGROUND AND PURPOSE: Spontaneous echocardiographic contrast (SEC) is correlated to clinical thromboembolic events. We sought to determine the origin of SEC by utilizing direct analysis of left atrial blood. METHODS: We examined the blood of 13 patients with and 19 without SEC. Blood samples were taken from the femoral vein and artery and from the right and left atria after transseptal puncture. Samples were incubated with fluorescence-labeled antibodies directed against the platelet (CD41a-PE, CD42b-PE, and CD62p-FITC) and leukocyte membrane epitopes (CD45-APC and CD14-FITC). The expressed epitopes were analyzed by dual laser flow cytometry immediately after blood withdrawal. RESULTS: In the peripheral blood of both groups, more activation and aggregation were found in the venous blood than in the arterial blood (CD41a, P=0.007; CD14neutro, P=0.017; and leukocyte-platelet aggregates [LTAg], P=0.002). In patients without SEC, the degree of activation and aggregation of the cardiac samples closely resembled the results of the peripheral samples. The degree of activation and aggregation was significantly higher in the right atrium than in the left atrium (LTAg, P<0.01; leukocyte activation, P<0.01; CD41a, P<0.01; CD62p, P<0.02). In contrast, in patients with SEC the parameters of platelet and leukocyte activation as well as LTAg was significantly higher in the left atrium than in the right atrium of the same patient (all P<0.01). A correlation between the amount of SEC and platelet-monocyte aggregates could be found (r=0.92, P<0.0001). CONCLUSIONS: The hypothesis that platelet aggregates are involved in the pathogenesis of SEC is supported by the fact that platelets in the left atrium of patients with SEC showed more activation.

[Tumor necrosis factor alpha in chronic heart failure. Clinical manifestation and therapeutic possibilities]. / Tumor-Nekrose-Faktor alpha bei chronischer Herzinsuffizienz. Klinische Manifestation und therapeutische Möglichkeiten.

BACKGROUND: Chronic heart failure (CHF) may be seen as a multi-system disorder with its origin in the heart but including many extracardiac manifestations. Immunological abnormalities are recognized in this context, in particular, changes in the expression of mediators of the innate immune response. IMPORTANCE OF TNF: Higher levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF) are found in the circulation and in the myocardium of patients with chronic heart failure than in controls. TNF has been implicated in a number of pathophysiological processes that are thought to be important to the progression of chronic heart failure. Therapies directed against this cytokine might therefore represent a novel approach to heart failure management.

MIC trial: metoprolol in patients with mild to moderate heart failure: effects on ventricular function and cardiopulmonary exercise testing.

UNLABELLED: Beta-blocker therapy results in a functional benefit in patients with heart failure (CHF) due to idiopathic dilated cardiomyopathy (DCM). This study assessed if similar effects were observed in patients with ischemic heart disease (CAD), NYHA II-III after 6 months of therapy with metoprolol. METHODS AND RESULTS: Fifty-two patients with CHF secondary to DCM (26 patients) and CAD (26 patients) and a left ventricular ejection fraction (EF)<40% were enrolled in the placebo-controlled study. The study medication was titrated over 6 weeks, the mean final dosage was 135 mg/day. Three patients died due to cardiogenic shock, two received placebo and one metoprolol. Eight patients did not complete the study due to non-compliance. Metoprolol significantly reduced heart rate at rest and after submaximal and maximal exercise. Vo(2)-max and Vo(2)-AT as well as the 6-min walk test improved significantly after metoprolol treatment. There was a significant increase in EF at rest (27.3-35. 2%), submaximal (28.5-37.7%) and maximal exercise (28.7-40.9%) in the metoprolol-treated patients. No differences were found between patients with CAD and DCM. We also observed reduced left ventricular volumes. CONCLUSION: The additional therapy with metoprolol improved cardiac function and the cardiopulmonary exercise capacity in patients with CHF.

Recombinant growth hormone therapy in patients with ischemic cardiomyopathy : effects on hemodynamics, left ventricular function, and cardiopulmonary exercise capacity.

BACKGROUND: We studied the effects of recombinant growth hormone (rhGH) on exercise capacity and cardiac function in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Seven patients (aged 55+/-9 years) with mild to moderate congestive heart failure (ejection fraction 31+/-4%) who were on standard therapy were included. The patients were studied at baseline, after 3 months of rhGH treatment, and 3 months after rhGH discontinuation. Cardiac function was assessed by exercise capacity, right heart catheterization at rest and after submaximal exercise, MRI, echocardiography, and Holter monitoring. When administered at a dose of 2 IU/d, rhGH doubled the serum concentration of insulin-like growth factor-I. rhGH improved clinical symptoms and exercise capacity significantly (New York Heart Association class 2.4+/-0.5 initially versus 1.4+/-0.5 at 3 months [mean+/-SD], P<0.05; VO2max 13.6+/-3.8 versus 17.4+/-5.4 mL. kg-1. min-1, P<0.05). Additionally, pulmonary capillary wedge pressures at rest and after submaximal exercise were reduced significantly. Cardiac output increased, particularly at rest (5.0+/-1.1 versus 5.8+/-1.3 L/min; P<0.05). Posterior wall thickness was increased (1.08+/-0.1 versus 1. 24+/-0.3 cm; P<0.05), and the end-diastolic and end-systolic volume indexes decreased significantly after rhGH treatment. There was no significant increase in left ventricular ejection fraction. The improvements were partially reversed 3 months after rhGH discontinuation. CONCLUSIONS: The administration of rhGH for 3 months in patients with ischemic cardiomyopathy results in significant improvement in hemodynamics and clinical function. The attenuation of left ventricular remodeling persisted 3 months after discontinuation of treatment.

[Determination of left ventricular mass by transthoracic three-dimensional echocardiography in patients with dilated cardiomyopathy]. / Linksventrikuläre Muskelmassenbestimmung bei Patienten mit dilatativer Kardiomyopathie mittels transthorakaler dreidimensionaler Echokardiographie.

Conventional echocardiographic methods of measuring left ventricular mass (LVM) are limited by assumptions of ventricular geometry and image plane positioning. Three-dimensional (3D) echocardiography offers a promising new approach for more accurate determination of LVM. This study was performed to compare LVM measurement by one- (1D), two- (2D), and 3D echocardiography with magnetic resonance imaging (MRI) in patients (pts) with dilated cardiomyopathy (DCM). 36 pts (age 18-74) with DCM underwent imaging by conventional 1D and 2D echocardiography as well as transthoracic 3D echocardiographic data acquisition. Also, pts were imaged with cardiac MRI. Due to echocardiographic and MRI quality and because of exclusion criteria's for MRI, it was not possible to accomplish each LVM determination method for each patient. LVM was determined by Devereux and area-length algorithm for the conventional echocardiography. 3D echocardiographic data was calculated after manual delineation of endo- and epicardial boundaries--slice by slice (5 mm)--in 3 perpendicular cut planes. LVM was determined by multiplying the myocardial volume by the specific density of the myocardium. To determine LVM in MRI, the even summation of slices method for myocardial volume measurement was used defined by the endo- and epicardium in short axis images. There was no significant correlation (r = 0.42) for measuring LVM between 1D echocardiography and MRI in pts with DCM. A significant correlation was obtained between 2D (r = 0.64, p < 0.01) echocardiography and MRI as well between 3D (r = 0.78, p < 0.01) and MRI in determination of LVM. Compared with 1D and 2D echocardiography, the 3D analysis achieved a significantly higher agreement with the results of the MRI (1D: 399.2 g, 2D: 285.9 g, 3D: 172.6 g versus MRI: 199.1 g). Interobserver variability was 5.1% for measuring LVM by 3D echocardiography (1D: 11.2%, 2D: 9.1%). In conclusion, in pts with DCM the determination of LVM was incompletely characterized by 1D and 2D echocardiography compared with results of MRI. The best correlation and high agreement for determination of LVM was obtained with 3D echocardiography compared with MRI.

High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril.

OBJECTIVES: To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.

Changes of neurohumoral parameters and endothelin-1 in response to exercise in patients with mild to moderate congestive heart failure.

UNLABELLED: Plasma endothelin levels are increased in patients with moderate and severe CHF. Conflicting data exist about the endothelin-1 (ET) level in patients with mild to moderate CHF and the effect of maximal exercise on plasma ET levels. METHODS AND RESULTS: We determined the plasma levels of ET and various neurohumoral parameters in 93 patients with CHF in functional class II and III of the NYHA classification at rest and after maximal bicycle exercise. Baseline ET level was increased compared to an age-matched healthy volunteer group (6.95+/-0.31 vs 3.29+/-0.17 pg/ml, mean+/-S.E.M., P<0.05), without significant differences between NYHA class II and III patients. Maximal exercise did not increase the ET level. In contrast, the neurohumoral parameters were significantly increased with maximal exercise. In conclusion, plasma levels of ET are increased in patients with mild to moderate CHF. However, no further increase in response to exercise was observed. Thus, it is highly unlikely that exercise capacity may be limited by ET-mediated peripheral vasoconstriction.