Implementation of pharmacotherapy guidelines in heart failure: experience from the German Competence Network Heart Failure.

AIM: To evaluate the implementation of current pharmacotherapy guidelines of heart failure and to identify factors associated with high pharmacotherapy guideline adherence in heart failure patients. METHODS AND RESULTS: We pooled data from seven studies performed in the context of the German Competence Network Heart Failure selecting patients with chronic systolic heart failure and left ventricular ejection fraction (LVEF) <45% (n = 2,682). The quality of pharmacotherapy was evaluated by calculating the guideline adherence indicator (GAI), which considers three (GAI-3) or five (GAI-5) of the recommended heart failure substance classes and accounts for respective contraindications. GAI-3 was categorized as perfect (GAI = 100%: 71% of the cohort), medium (GAI = 50-99%: 22%), and poor adherence (GAI <50%: 7%). In ordinal regression, the following factors were positively associated with perfect adherence: history of revascularization (odds ratio 1.59, 95% confidence interval 1.27-1.98), prior ICD implantation (2.29, 1.76-2.98), and LV ejection fraction <30% (1.45, 1.19-1.76), whereas age (per 10 years; 0.82, 0.77-0.89), NYHA III/IV (0.15, 0.12-0.18), unknown duration of heart failure (0.69, 0.53-0.89), and antidepressant medication (0.61, 0.42-0.88) were negatively associated with perfect adherence. Better GAI-3 at baseline predicted favorable changes of LV ejection fraction and end-diastolic diameter after 1 year. One-year mortality risk was closely related to GAI-3 in both groups of NYHA functional class I/II (excellent vs. poor GAI-3: 7.2 vs. 14.5%, log rank = 0.004) and class III/IV (13.5 vs. 21.5%, log rank = 0.005). CONCLUSIONS: This large pooled analysis showed that a high level of guideline adherence is achievable in the context of clinical studies. Those receiving and tolerating optimal pharmacotherapy experience a better prognosis. Nevertheless, the implementation of heart failure medication needs further improvement in female and elderly patients, especially those in NYHA functional class >II and patients with LVEF ≥30%.

Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with Type 2 diabetes and impaired glucose tolerance undergoing coronary angiography.

AIMS: Left ventricular diastolic dysfunction is considered a precursor of diabetic cardiomyopathy, while diabetic cardiovascular autonomic neuropathy is associated with an increased risk of mortality. This study aimed to evaluate the association between left ventricular diastolic dysfunction and cardiovascular autonomic neuropathy, both diagnosed according to the current guidelines. METHODS: We evaluated 145 patients referred for an elective coronary angiography, 52 of whom had Type 2 diabetes and 48 had impaired glucose tolerance, while 45 subjects had normal glucose tolerance. Cardiovascular autonomic neuropathy was diagnosed using autonomic function tests, while left ventricular diastolic dysfunction was verified by tissue Doppler imaging echocardiography. RESULTS: Cardiovascular autonomic neuropathy was diagnosed in 15 (28.8%) patients with Type 2 diabetes and in six (12.5%) individuals with impaired glucose tolerance. The rates of left ventricular diastolic dysfunction were 81 and 33% in patients with and without cardiovascular autonomic neuropathy, respectively (P < 0.001). In the cardiovascular autonomic neuropathy group (n = 21), early diastolic relaxation velocity (Em) was significantly reduced (5.4 ± 0.9 vs. 7.3 ± 2.1 cm/s; P < 0.001) and the E/Em ratio was significantly higher (13.6 ± 4.6 vs. 10.3 ± 3.4 cm/s, P < 0.001) as compared with the group without cardiovascular autonomic neuropathy (n = 79). These findings remained significant after adjustment for age, sex, coronary artery disease, hypertension and HbA(1c) . A severe form of left ventricular diastolic dysfunction was observed in 33 and 15% of patients with and without cardiovascular autonomic neuropathy, respectively (P = 0.001). CONCLUSION: Cardiovascular autonomic neuropathy is associated with a higher prevalence and a more severe form of left ventricular diastolic dysfunction in patients with diabetes or impaired glucose tolerance undergoing coronary angiography. Because both cardiovascular autonomic neuropathy and left ventricular diastolic dysfunction are associated with increased cardiovascular morbidity and mortality, screening for patients with left ventricular diastolic dysfunction and cardiovascular autonomic neuropathy with diabetes or impaired glucose tolerance may identify those at high risk.

Newly detected glucose disturbance is associated with a high prevalence of diastolic dysfunction: double risk for the development of heart failure?

Diastolic dysfunction is associated with a high rate of morbidity and mortality and has a high prevalence in patients with diabetes. Aim of the study was to investigate the prevalence of diastolic dysfunction in patients with newly detected glucose metabolism disorder (GMD) submitted for coronary angiography. Oral glucose tolerance test, echocardiography, and tissue Doppler imaging were performed in patients referred to coronary angiography. Prevalence of diastolic dysfunction was 97, 88, and 74% in the known diabetes, newly detected diabetes, and new diagnosed impaired glucose tolerance group, respectively. This is higher than previously reported. Severity of diastolic dysfunction was associated with higher 2-h plasma glucose levels and with new diagnosed diabetes. Screening patients with newly detected GMD for diastolic dysfunction may identify patients with double risk for cardiovascular morbidity and mortality and this group might be a target population to avoid development heart failure.

Plasma levels of NT-pro-BNP in patients with atrial fibrillation before and after electrical cardioversion.

OBJECTIVE: Plasma levels of brain natriuretic peptide (BNP) have been examined in studies on patients with persistent atrial fibrillation, both before and after electrical cardioversion. Studied patients often showed a comorbidity with congestive heart failure, which complicates interpretation of measured BNP values as a natriuretic peptide. The aim of this study was to examine plasma levels of N-terminal fragment pro-brain natriuretic peptide (NT-pro-BNP), which is the more stable but inactive cleavage product of pro-BNP in patients with atrial fibrillation, but normal left ventricular ejection fraction, before and after electrical cardioversion. PATIENTS AND METHODS: NT-pro-BNP plasma levels of 34 consecutive patients were measured before, shortly after and 11 days after electrical cardioversion. All patients showed a normal ejection fraction after echocardiographic or laevocardiographic criteria. RESULTS: At baseline, all patients showed elevated NT-pro-BNP compared to a healthy control group (1086 vs. 66.9 pg/ml, p<0.001). After a mean follow-up time of 11 days in patients with persistent restored sinusrhythm, NT-pro-BNP decreased from 1071 pg/ml at baseline to 300 pg/ml (p<0.001). In contrast, patients with recurrence of atrial fibrillation showed increased levels from 1570.5 pg/ml at baseline to 1991 pg/ml (p=0.13; n.s.). Recurrence of atrial fibrillation was independent from height of NT-pro-BNP levels at baseline (p=0.23). CONCLUSIONS: Atrial fibrillation in patients with a normal left ventricular ejection fraction is associated with elevated NT-pro-BNP plasma levels, which decrease when a persistent sinus-rhythm can be restored by electrical cardioversion. On the other hand, NT-pro-BNP seems to increase (n.s.) when recurrence of atrial fibrillation occurs. Finally, NT-pro-BNP is no valid predictor for long-term success of sinus-rhythm restoration by electrical cardioversion.

Frequency and quantity of the parvovirus B19 genome in endomyocardial biopsies from patients with suspected myocarditis or idiopathic left ventricular dysfunction.

Parvovirus B19 (PB19) has been identified as a possible cause of myocarditis and heart failure in both children and adult patients. This study used real time PCR analysis, to determine the frequency and to quantify PB19 viral genomes in endomyocardial tissue samples from 80 adult patients with clinically suspected myocarditis or idiopathic left ventricular dysfunction and from 36 controls. Histological (Dallas classification) and immunohistological analyses were performed to detect myocardial inflammation in the endomyocardial biopsies.PB19 genomic DNA was found in nine of 80 patients (11.2%), 4 out of 31 (12.9%) patients with inflammatory infiltrates detected via immunohistological methods and 5 out of 49 (10.2%) patients with left ventricular dysfunction without myocardial inflammation. The copy numbers for PB19 DNA ranged between 30 and 3900 per microg of cellular DNA. Four patients with clinically suspected myocarditis had copy numbers for PB19 DNA of 70, 740, 3400 and 3900, respectively, per microg of cellular DNA in the endomyocardial biopsy. Five patients with idiopathic left ventricular dysfunction had copy numbers for PB19 DNA of 30, 38, 52, 58 and 90, respectively, per microg of cellular DNA in the endomyocardial biopsy. The amplicon of one of the nine positive PCR fragment was sequenced and was found to be fully identical in the highly conserved sequence of published Parvovirus B19 VP1/VP2 genes (NCBI gene bank). In all patients, acute myocarditis was excluded according to the Dallas classification. All biopsies of 36 controls with no history of myocarditis or recent viral infection were negative for myocardial inflammation and parvovirus B19 genomes. In summary, Parvovirus B19 DNA is present within the myocardium of patients with suspected myocarditis and idiopathic left ventricular dysfunction and can be detected and quantified in endomyocardial specimens via real time PCR.

Detection of Helicobacter pylori specific DNA in human atheromatous coronary arteries and its association to prior myocardial infarction and unstable angina.

BACKGROUND: Chronic infections have been proposed to play a role in the aetiology or progression of atherosclerotic plaques. Increased risk of coronary artery disease has been suggested in patients seropositive for Helicobacter pylori. AIM: To analyse coronary specimens in patients with severe (coronary artery disease) for Helicobacter pylori specific DNA. PATIENTS AND METHODS: Atherosclerotic plaques were obtained in 46 consecutive patients (9 female, 37 male, mean age 62.7+/-9.17 years) during coronary bypass procedures. Serum was analysed for IgG -/cagA-antibodies specific for Helicobacter pylori. Polymerase chain reaction and sequence analysis were used to identify bacterial DNA. Coronary artery biopsies from 19 autopsies without coronary artery disease were examined as a control group. RESULTS: Of the 46 coronary artery disease patients, 32 (69.6%) were Helicobacter pylori seropositive. Positive results for Helicobacter pylori DNA showed 18 seropositive and 4 seronegative (with anamnesis of eradication therapy). A total of 22 patients (47.8%) of the coronary artery disease group but none of controls revealed positive DNA. In the coronary artery disease group, a correlation between DNA presence and prior myocardial infarction (p=0.008) and unstable angina (p<0.001) was found. CONCLUSION: Identification of DNA in atherosclerotic plaques of patients with severe coronary artery disease supports the hypothesis that Helicobacter pylori infection may influence the development of atherosclerosis. Our results may indicate an direct involvement of Helicobacter pylori in the progression and instability of plaques in these patients.

[Genetics of dilated cardiomyopathy]. / Genetik der dilatativen Kardiomyopathie.

Dilated cardiomyopathy is one of the leading causes of heart failure and a primary cause for heart transplantation in patients below the age of 40 years. Despite major advances in diagnostic procedures such as examination of myocardial biopsies, the etiology remains unknown in many patients. Chronic inflammation or myocarditis and chronic alcohol abuse are considered two main etiologic factors in dilated cardiomyopathy. A third causal factor, namely genetic transmission of the disease, is at least as common as myocardial inflammation or toxic damage. Several prospective studies of relatives of patients with dilated cardiomyopathy proved that about 25-30% of all cases are of familial etiology. The most common mode of inheritance is autosomal dominant. Less frequently is the disease inherited as an X-chromosomal trait. Autosomal recessive and mitochondrial transmission is rare. The penetrance is highly variable and age dependent. Many relatives of patients with DCM show only minor cardiac abnormalities and it is unknown whether they progress to full cardiomyopathy in later life. Examination of families has identified so far eight disease genes, namely the dystrophin, tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta-myosin heavy chain, and cardiac troponin T gene. Certain mutations in lamin A/C cause conduction system disease and dilated cardiomyopathy, whereas other mutations cause in addition skeletal muscle myopathy. Dystrophin mutations are the cause of the rare X-linked dilated cardiomyopathy without skeletal muscle involvement and a progressive course in young men. Other mutations in the dystrophin gene, mainly deletions, are the cause of the muscular dystrophy Becker and Duchenne which also present with dilated cardiomyopathy. Mutations of the desmin, delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as well as the troponin T gene are known to cause autosomal dominant-dilated cardiomyopathy without other abnormalities. The infantile X-linked DCM is caused by mutations of the tafazzin gene. The onset of the disease is typically within the first year of life and death occurs usually in childhood. Most patients may in addition be characterized by skeletal myopathy, short stature, neutropenia and abnormal mitochondria, also referred to as Barth syndrome. Knowledge of the DCM disease genes led to the new hypothesis that dilated cardiomyopathy is a disease of the myocardial force generation or force transmission. Many more disease loci are known but the responsible disease genes are not yet identified. Better understanding of the expression and function of disease genes may eventually result in new diagnostic and therapeutic tools in order to improve the prognosis of this severe disorder.

[New strategies in the treatment of restenosis]. / Neue Strategien zur Behandlung der Restenose.

Twenty-three years after introduction of coronary angioplasty (PTCA), the inhibition of restenosis formation continues to be the major challenge for the interventional cardiologist. About 35-50% of all patients undergoing PTCA develop a renarrowing of the intravascular lumen within the following six months. The use of specific systemic drug therapy as well as different angioplastic methods (rotablation, atherectomy, laser angioplasty) all failed to significantly reduce restenosis. Local drug delivery and local gene therapy have only shown to be effective in animal experiments. Restenosis can be reduced by the use of stents; however restenosis can also develop within the stents. The treatment of choice for severe in-stent restenosis may become radiotherapy, which seems to be a promising tool also for other forms of restenosis.

The effect of leukocyte-depleted blood cardioplegia in patients with severe left ventricular dysfunction: a randomized, double-blind study.

BACKGROUND: The propensity for leukocytes to cause reperfusion injury in patients undergoing heart surgery is widely accepted. Reperfusion injury may result in myocardial damage and unfavorable operative outcome, especially in patients with severely reduced ejection fractions. This study was performed to evaluate the impact of leukocyte filtration on the postoperative course of patients undergoing coronary bypass surgery. METHODS: Thirty-two patients with coronary artery disease and left ventricular ejection fraction less than 35% were included in this double-blind, randomized study. Two serial leukocyte removal filters (Pall BC1B filter [Pall Biomedical, Portsmouth, England], group F, 15 patients) or two dummy filters (group C, 17 patients) were connected to the blood cardioplegia line. Leukocyte count, hemodynamic measurement, and transesophageal echocardiography were performed before and after cardiopulmonary bypass. Cardiac-specific enzymes were analyzed from arterial blood during the first 72 hours and from coronary sinus blood 30 and 60 minutes after aortic unclamping. RESULTS: Patient characteristics were similar in the two groups (ejection fraction 20.9% +/- 4.3% in group C and 21.1% +/- 4.8% in group F; P =.773). No early death or perioperative myocardial infarction occurred. Leukocyte count, hemodynamic parameters, cardiac troponin T, cardiac troponin I, and creatine kinase MB mass levels in arterial blood were similar in the two groups. Group F showed lower release of cardiac troponin T from the coronary sinus 30 minutes after unclamping of the aorta (group F, 0.263 +/- 0.12 ng/mL; group C, 0.6 +/- 0.32 ng/mL; P =.005). Lower doses of dopamine were necessary after cardiopulmonary bypass (group F, 0.36 +/- 0.11 mg x kg(-1) x min(-1); group C, 0.49 +/- 0.14 mg x kg(-1) x min(-1); P =.003). A moderate increase in ejection fraction was observed at 30 minutes in both groups (group F, 30.3% +/- 6.2%; group C, 28.0% +/- 6.3%; P =.239) and a significant increase at 60 minutes in group F (group F, 32.5% +/- 6.0%; group C, 27.4% +/- 7.5%; P =.012). CONCLUSIONS: These results indicate that serial leukocyte filters connected to the blood cardioplegia line decrease myocardial cell injury and may therefore help to improve outcome of patients with severely depressed ejection fractions undergoing coronary artery bypass grafting.

[New strategies to treat restenosis]. / Neue Strategien zur Behandlung der Restenose.

Twenty-three years after introduction of coronary angioplasty (PTCA), the inhibition of restenosis formation continues to be the major challenge for the interventional cardiologist. About 35-50% of all patients undergoing PTCA develop a renarrowing of the intravascular lumen within the following six months. The use of specific systemic drug therapy as well as different angioplastic methods (rotablation, atherectomy, laser angioplasty) all failed to significantly reduce restenosis. Local drug delivery and local gene therapy have only shown to be effective in animal experiments. Restenosis can be reduced by the use of stents; however restenosis can also develop within the stents. The treatment of choice for severe in-stent restenosis may become radiotherapy, which seems to be a promising tool also for other forms of restenosis.

Development and characterization of a rapid assay for bedside determinations of cardiac troponin T.

BACKGROUND: The appearance of cardiac proteins in blood is the most specific and sensitive indicator of acute myocardial cell necrosis. The measurement of cardiac markers, however, is time consuming and requires sophisticated equipment. To facilitate the biochemical detection for acute myocardial cell necrosis, a whole-blood rapid assay device for cardiac troponin T detection was developed that provides a test result within 20 minutes. METHODS AND RESULTS: Monoclonal antibody M7 is labeled with gold particles, and antibody 1B10 is labeled with biotin. Both antibodies, as well as buffer substances and detergents, are adsorbed onto paper fleeces mounted below an application well. Heparinized blood (160 microL) applied to this well solubilizes the dry chemistry reagents. Blood cells are separated from plasma via a glass-fiber fleece. The immunocomplexes formed are concentrated within the reading zone by binding of the biotin-labeled antibody with streptavidine immobilized to the test device. Troponin T bound to the test device serves as a control. The detection limit of this assay is 0.18 microgram/L with a cross-reactivity with skeletal troponin T of 0.5%. In clinical analyses involving 25 healthy volunteers, 62 patients with chest pain but without myocardial ischemia, 35 patients with acute myocardial infarction, 24 patients with minor myocardial cell damage due to radiofrequency ablation, and 35 patients with unstable angina, the rapid assay was comparable to the troponin T enzyme immunoassay in regard to sensitivity and specificity. CONCLUSIONS: This newly developed assay allows accurate, rapid, and convenient diagnosis of acute myocardial cell necrosis.

Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium.

Ischemia is known to produce damage to subcellular organelles, such as nuclei and mitochondria, in myocardial tissue. We tested the hypothesis that during myocardial ischemia various cytoskeletal and contractile proteins also undergo changes. We induced total global ischemia by incubation in buffer of tissue samples from six human left ventricles that were obtained from heart transplant recipients. Samples were removed from the incubation medium at different time intervals and investigated by immunohistochemistry using monoclonal antibodies against myosin, actin, tropomyosin, troponin T, myomesin, desmin, tubulin, and vinculin. The degree of ischemic injury was determined by electron microscopy. Ischemic cardiomyopathic human tissue showed disturbances of the localization pattern of myosin, actin, tropomyosin, and troponin T as early as 10 minutes after the onset of ischemia; this disruption was complete at 20 minutes. Tubulin also started changing at 10 minutes, but complete disruption was only evident after 120 minutes. Desmin and myomesin showed an intermediate response; changes began at 30 to 40 minutes, and disruption was complete at 90 to 120 minutes. Vinculin was most resistant to ischemia. Ultrastructurally, the tissue showed moderate reversible ischemic injury during the entire period of 180 minutes. Measuring the exposure time in seconds allowed quantitation of the intensity of the fluorescence. We reached the following conclusions: (1) Ischemia causes damage to the contractile proteins sooner than to the cytoskeleton and subcellular organelles. (2) Diseased human hearts are extremely susceptible to the effects of ischemia. These findings are important for the situation of induced cardiac arrest in heart operations and for preservation of donor hearts for transplantation.

X-linked dilated cardiomyopathy. Novel mutation of the dystrophin gene.

We report on a family with a severe form of X-linked dilated cardiomyopathy (DCM). Two brothers, the elder requiring heart transplantation, and a maternal cousin presented elevated creatine kinase levels, increased right ventricular diameters and electrocardiographic abnormalities. All complained of exertional cramping myalgia, but none had muscle weakness or a pathological electromyogram. Muscle biopsies of these individuals revealed a mild myopathic picture with atrophic type I and hypertrophic type II fibers. Immunofluorescence using N- and C-terminal antibodies (dys-2, dys-3) against the dystrophin protein showed preserved, but reduced intensity of staining of the sarcolemmal membranes. Using the same two antibodies, Western blot analyses revealed a dystrophin molecule of the expected molecular weight, which was quantitatively reduced by 80%. However, the dys-1 antibody, directed against the mid rod region of the dystrophin protein, did not react with dystrophin both on Western blot and immunofluorescence. Linkage analysis with polymorphic markers of the dystrophin gene revealed an identical haplotype at the 5' region in all affected individuals (two point lod score of 1.93, phi = 0). A deletion of exons 48, 45-53, 2-7 and 1 including the promoter region of the dystrophin gene, as described in rare cases with similar clinical signs could be excluded by multiplex PCR and Southern blot analyses of this DCM family. In addition, a major splice-mutation of dystrophin mRNA was excluded by RT-PCR of skeletal and heart muscle tissue. Therefore, we conclude that a novel mutation in the 5' region of the dystrophin gene phenotypically leads to this severe form of DCM. Extensive analyses of the dystrophin gene, in particular of the sequences coding for the antigenic determinants of the dys-1 antibody in the mid rod region, may identify the molecular cause of this monogenetic form of DCM.

Intracellular compartmentation of troponin T: release kinetics after global ischemia and calcium paradox in the isolated perfused rat heart.

The marked differences in troponin T serum concentrations observed in patients with reperfused and non-reperfused myocardial infarction may be due to a perfusion dependent wash-out of an unbound fraction of cardiac troponin T. To test the release kinetics of troponin T experimentally, the isolated rat heart (Langendorff preparation) was damaged either by the calcium paradox or by no-flow ischemia. Following membrane damage by the calcium paradox troponin T (TNT) showed the same release kinetics in the coronary effluent as the cytosolic markers creatine kinase (CK) or lactate dehydrogenase (LDH). Peak levels of troponin T (282 +/- 58 micrograms/l), CK (6754 +/- 1642 U/l), and LDH (5817 +/- 1730 U/l) occurred 5 min after onset of reperfusion with calcium containing buffers and returned to 9.9%, 1.3%, and 1% of their respective peak levels within 55 min of reperfusion. During reperfusion after no-flow ischemia different release kinetics were found for cytosolic enzymes and troponin T. After 60 min of ischemia, troponin T levels in the coronary effluent increased over the entire reperfusion period of 55 min, almost doubling the 5 min value (191%). In contrast, cardiac enzymes rapidly declined to 18% (CK) and 23% (LDH) of their respective 5 min values at the end of reperfusion. Light microscopy after reperfusion with carbon black revealed a complete and homogeneous reperfusion of Langendorff hearts after no-flow ischemia. Immunoblot analysis confirmed the release of an undegraded 39 kDa troponin T molecule, both after global ischemia and the calcium paradox. These data indicate that prolonged ischemia induces a continuous liberation of cardiac troponin T, most probably from disintegrating myofibres, whereas membrane damage leads almost exclusively to leakage of a functionally unbound troponin T pool. These findings may explain the biphasic serum concentration changes of cardiac troponin T in patients with reperfused myocardial infarction.

[Clinical aspects and follow-up in dilated cardiomyopathy]. / Klinik und Verlauf der dilatativen Kardiomyopathie.

Dilative cardiomyopathy is a heterogeneous myocardial disease characterized by a depressed contractile function and ventricular dilation. The exercise intolerance of patients with dilative cardiomyopathy is partly explained by changes of metabolism and composition of skeletal muscle, whereas the physical findings result from progressive heart failure and cardiac remodeling. The clinical course of the disease is highly variable and prognostic indicators of progressive heart failure or cardiac arrhythmias are of little value in the assessment of cardiac risk in an individual patient. During recent years the mortality of patients with dilative cardiomyopathy was 5-15%, which appears to be lower than previously reported. The differences in mortality today and in previous years may be explained by a more precise and earlier diagnosis of the disease and possibly better treatment strategies. Patients with a severely depressed left ventricular function but a stable clinical course, a good hemodynamic response to therapy, and an oxygen uptake of > 12 ml/kg min can be followed without heart transplantation. It can be expected that the definition of the molecular causes of dilative cardiomyopathy will lead to a better classification of the patients and the development of more efficient treatment strategies.

Assessment of reperfusion of the infarct zone after acute myocardial infarction by serial cardiac troponin T measurements in serum.

BACKGROUND: The purpose of this study was to derive indices of reperfusion and non-reperfusion after acute myocardial infarction (AMI) from changes in serum concentrations of cardiac troponin T and to test the predictive value of these indices. METHODS: The indices were derived from a retrospective analysis of changes in serum troponin T concentration in 71 patients given thrombolytic treatment who had immediate and late angiography (group 1). These troponin T indices were first tested in a blinded and prospective study of 53 consecutive patients eligible for thrombolytic therapy (group 2). They were then used for the non-invasive assessment of reperfusion of AMI in 48 patients (group 3). RESULTS: In group 1 troponin T serum concentration curves were biphasic in patients who had reperfusion < or = 5.8 h after the onset of symptoms. Release of the cytosolic troponin T pool resulted in a peak at 14 h and ended at 38 h. The probability of reperfusion was > 95% when the ratio of peak cytosolic troponin T concentration to concentration at 38 h (PV1/38) exceeded 1.42 or the ratio of troponin T concentration at 14 h to that at 38 hours (14/38) exceeded 1.09. The probability of the presence of non-reperfused AMI was < 5% when troponin T PV1/38 and 14/38 ratios were < 0.99 and < 0.84 respectively. These discriminatory values of troponin T indices correctly classified (efficiency 96%) 48 of the 53 group 2 patients in whom immediate and late angiography were performed. When troponin T indices were used to classify 48 group 3 patients who were not studied by immediate angiography, thrombolytic therapy was deemed to have been successful in 82% of the treated patients, with spontaneous recanalisation in 11% and 23% of the non-treated patients assessed by PV1/38 and 14/38 respectively. CONCLUSION: The PV1/38 or 14/38 ratios of serum troponin T concentration indicated the effectiveness of thrombolytic therapy in achieving reperfusion of AMI.

[Modification of re-stenosis with drugs]. / Medikamentöse Beeinflussung der Re-Stenosierung.

In the treatment of patients with symptomatic coronary artery disease using PTCA, success is limited due to restenosis rates ranging from 30-50% of the lesions treated. Medical approaches to reduce the rate of restenosis were therefore tested in a number of trials. However, in only a few randomized and controlled trials were positive effects reported. Inhibiting platelet aggregation through the use of anti-glycoprotein IIb/IIIa monoclonal antibody 7E3 and, in some studies, with 3 omega fatty acids, a significant reduction in the rate of restenosis was observed. Many trials testing less potent inhibitors of platelet aggregation, such as acetylsalicylic acid, prostacyclin, thromboxane A2 receptor antagonists, and ticlopidine as well as anticoagulants such as heparin or coumarin, calcium antagonists, ACE-inhibitors, antiproliferative agents such as colchicine, methylprednisolone, and angiopeptin were inconclusive or without a positive treatment effect. The results of a hirudin multicenter trial on the rate of restenosis (Helvetica Trial) will soon be reported. There are many possible reasons for these disappointing results, such as poor standardization of the invasive studies, in analyzing the degree of coronary artery stenoses, the inadequate sample size in many trials, and insufficient local drug concentrations as well as the lack of beneficial effects of the study medication. Thus, at present there is no effective treatment to reduce the restenosis rate following PTCA. However, it can be expected that potent antithrombins, or inhibitors of platelet aggregation, may be useful.

[Monitoring ischemia with new markers]. / Ischämiemonitoring mit neuen Markern.

The measurement of cardiac enzymes is critical for the diagnosis of acute myocardial infarction. Cardiac enzymes, however, are by no means ideal marker molecules, primarily due to their non-specific tissue distribution and low concentration in cardiomyocytes. Many limitations of cardiac enzymes can be overcome by the measurement of cardiospecific troponin T or I with immunological techniques. In the evaluation of new diagnostic methods it is important to define the purpose of marker molecule measurement, i.e., monitoring of definite myocardial infarction or establishing the proper diagnosis in patients with suspected myocardial infarction. For monitoring of success of reperfusion therapy and for the detection of reocclusion short-lived perfusion markers with rapid appearance in circulation such as myoglobin, fatty acid binding protein or glycogenisophosphorylase BB are preferable. For proper diagnosis in patients with suspected acute myocardial infarction test systems with high sensitivity and specificity are needed due to the low prevalence of disease in the patients tested. Troponin T determinations are particularly useful in this group of patients. With troponin T determinations it could be shown that some patients so far classified as having unstable angina do in fact have microinfarction. These data indicate the need for re-definition of diagnostic criteria of acute myocardial infarction.

[Myocardial infarct: acute intervention]. / Der Myokardinfarkt: akute Intervention.

Treatment strategies in acute myocardial infarction are directed toward limitation of infarct size and reduction of frequency of complications. This goal is best achieved by early reperfusion of ischemic myocardium. All trials comparing thrombolytic treatment in acute myocardial infarction indicate that either streptokinase, APSAC, or rtPA reduce mortality significantly. Particularly patients at high risk (old patients, women) benefit most from thrombolytic treatment. Although, conservation of left ventricular function and risk reduction is best achieved by very early treatment, a reduction of mortality has even been shown if thrombolytic agents are if given before 12 hours after onset of symptoms. Primary PTCA is an attractive alternative to thrombolytic therapy particularly in patients with anterior wall myocardial infarction or cardiogenic shock. Routine PTCA early or late after thrombolytic treatment however does not alter the outcome of the patients. The value of rescue PTCA remains to be settled. Heparin as an adjunctive treatment of rtPA improves patency of the coronary arteries and reduces mortality. Newer anti-thrombotic agents like hirudin, argotraban, or monoclonal antibody 7E3 are even more promising for prevention of reocclusion after thrombolytic treatment. Of the conservative medical treatment aspirin, beta-blockade, nitrates, and magnesium all have been shown reduce mortality. Similar effects could not be proven for calcium antagonists or routine antiarrhythmic drugs. ACE-inhibitors are of value if given 3 days after onset of symptoms.