Biomarkers in acute coronary syndrome and percutaneous coronary intervention.

The universal definition of myocardial infarction has proved how important the role of biomarkers in the assessment of acute coronary syndrome (ACS) has become. As a result, management of patients with ACS today is more specific and personalized than ever, but there is still a lot of room for improvement. Unmet needs for a faster and more specific rule-in and rule-out of myocardial infarction, for a pronounced risk assessment allowing for standardized guidelines on personalized therapy and for an effective monitoring of our therapeutic efforts to guarantee an optimal risk-benefit turnout still require intensive biomarker research and clinical validation. This review addresses a set of cardiovascular biomarkers with different pathophysiological backgrounds and discusses their diagnostic, prognostic and therapeutic value in the setting of ACS and percutaneous coronary intervention (PCI). The article provides a review of the current knowledge and literature on biomarkers in ACS and PCI, discussing currently used biomarkers like cardiac troponin (cTN), high sensitive cardiac troponin (hscTn), natriuretic peptides (NPs) as well as promising future biomarkers like copeptin, choline and lipoprotein-associated phospholipase A2 (LP-PLA2). The review concentrates on the clinical application of these markers, evaluating not only their diagnostic and prognostic value but also their integrability into routine practice. There are currently a number of new biomarkers and new biomarker assays under investigation which give hope for a much improved diagnostic and risk stratification process. Large diagnostic clinical trials are still needed to evaluate their impact on ACS patient management and subsequent PCI in clinical practice.

Clinical and biological impact of antiretroviral therapy with protease inhibitors on HIV-related Kaposi's sarcoma.

OBJECTIVE: To evaluate the clinical and biological impact of protease inhibitors on HIV-associated Kaposi's sarcoma. DESIGN AND SETTING: A cohort of 10 patients included prospectively from April 1996 to June 1997 were studied in one institutional centre after initiation of protease inhibitors. PATIENTS AND METHODS: All patients but one (stable disease) had progressive Kaposi's sarcoma. Three out of 10 patients had stopped specific chemotherapy for Kaposi's sarcoma for more than 4 weeks, three were still under chemotherapy, and four had never received specific treatment of Kaposi's sarcoma. Plasma HIV viral load, human herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and CD4 cell count were sequentially assessed from the beginning of therapy. For six patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposi's sarcoma lesions was performed during treatment using polymerase chain reaction. RESULTS: After initiation of HIV triple therapy with protease inhibitors, we observed six complete responses, two partial responses, and two patients with progressive disease. All patients had undetectable plasma HIV viral load within 2 months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of eight patients with partial or complete response and in none of the progressive patients. A decrease or negation of HHV-8 viral load in Kaposi's sarcoma lesions was observed in two complete responders. CONCLUSION: Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposi's sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.

Reference values for cardiac troponins I and T in a goal-oriented concept of health: cardiac marker values in a series of outpatients without acute coronary syndromes.

BACKGROUND: Cardiac troponins are part of the new definition of acute myocardial infarction (AMI) by the European Society of Cardiology and the American College of Cardiology (ESC/ACC). In the new guidelines, it was suggested to establish reference values for cardiac troponins to calculate the 0.99 quantile (Q99) as cutoff for AMI diagnosis. PATIENTS AND METHODS: We run a prospective series of troponin measurements in unselected outpatients who had no suspicion of cardiac ischemia. The selection of patients as reference population is based on a "goal-oriented concept of health". One hundred and ninety-five patients agreed that 10-ml additional blood was drawn at the occasion of the venous puncture done routinely in the evaluation of their case. Cardiac troponin I was measured using a point of care (POCT) device (Stratus CS, DadeBehring, TNI-PO). Additionally, heparin-plasma was obtained and immediately deep-frozen to -80 degrees C for later batch measurement of cardiac troponin T (Elecsys 2010, Roche Diagnostics, TnT) and troponin I (Centaur, Bayer, TnI-CL). RESULTS: The Q99 values were 0.14 microg/l for TnI-PO, 0.023 microg/l for TnT and 0.07 microg/l for TnI-CL in patients with creatinine levels below 1.5 mg/dl. These values lay above those obtained from people at good health for reference study purposes. On the level of our cutoffs, CVs were 7.5%, 6.4% and 23.7% for TnI-PO, TnT and TnI-CL, respectively. CONCLUSIONS: Only the TnI-PO and TnT tests fulfilled the imprecision criteria in our study. TnI-PO values between 0.10 and 0.14 microg/l and TnT values between 0.01 and 0.03 microg/l have to be interpreted carefully. Patients presenting with chest pain will be possibly true positives, but patients without chest pain and nondiagnostic ECGs should be subjected to repetitive troponin measurements and further noninvasive investigation and maybe not directly sent to the cardiac catheter laboratory.

The acute coronary syndrome diagnosis and prognostic evaluation by troponin I is influenced by the test system affinity to different troponin complexes.

It was suggested recently that cardiac troponins are released as T-I-C complexes and then further degraded to T and I-C. It is not known whether the various affinity to the T-I-C and I-C complex of different troponin I test systems influence the diagnostic and prognostic value of the test results in clinical practice. We studied 162 patients (61.3 S.D. 11.1 years) with suspected acute myocardial infarction (AMI) in a single center study. AMI was confirmed in 109 patients. Blood samples were taken at admission, after 1, 2, 4, 8, 12 and 24 h. Troponin I (TnI) was measured using the OPUS plus (TnI-O, cut-off 1.6 microg/l) and the Stratus II (TnI-S, cut-off 1.5 microg/l) analyzers. TnI-O has high affinity to the binary (I-C) and TnI-S to the ternary (T-I-C) troponin complex. A 6-month follow-up with respect to death and recurrent AMI was performed. The sensitivity (SE) and specificity (SP) for AMI diagnosis were 82.6 and 86.8% for TnI-S; 75.2 and 92.5% for TnI-O 0-2 h after admission. The ROC analysis showed a slightly better curve for TnI-S at 4 h (P<0.05). Logistic regression analysis shows prediction of 6 months outcome by 0-24 h serial TnI-S measurements (odds ratio 5.21, P=0.0356), and serial TnI-O measurements (odds ratio 4.92, P=0.0186). High affinity to the ternary troponin complex enhances the diagnostic but not the prognostic value of a test system. Indeed, the resulting differences are small but underline the need for standardization of biochemical markers.

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes.

BACKGROUND: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

[Effect of smoking on relaxation and filling behavior of the left ventricle in healthy probands. An echocardiography study]. / Einfluss des Zigarettenrauchens auf Relaxation und Füllungsverhalten des linken Ventrikels bei Herzgesunden. Eine echokardiographische Untersuchung.

UNLABELLED: To examine the impact of acute nicotine consumption echocardiographic examination was performed in 22 healthy subjects (nine women, 13 men, 20 to 50 cigarettes/day over a minimum of five years) without any evidence of organic heart disease (normal 2D and Doppler echo, normal ECG at rest and during exercise) aged 20 to 51 years (mean +/- SD: 37 +/- 9 years) before and after cigarette smoking (0.9 mg nicotine). Left ventricular filling parameters were derived by transmitral pulsed Doppler ultrasound with the flow profile along the mitral valve being characterized by the early diastolic (E-wave) and late diastolic (A-wave) inflow into the left ventricle. The isovolumetric relaxation period was determined by simultaneous M-mode registrations over the aortic and mitral valve. During smoking the early diastolic peak velocity decreased from 56 to 52 cm/s (p less than .01) and the early diastolic flow integral fell from 64 to 56 mm (p less than .01). The A/E ratio of the peak velocities rose from 68 to 82% (p less than .001), the A/E ratio of the flow integrals increased from 46 to 56% (p less than .001) and the atrial contribution to ventricular filling rose from 33 to 36% (p less than .001). Furthermore during cigarette smoking the isovolumetric relaxation period rose from 70 to 77 ms (p less than .001). - CONCLUSION: In healthy subjects cigarette smoking causes an increase of the atrial contribution to ventricular filling and the isovolumetric relaxation period. Thus, acute nicotine consumption significantly impairs the energy-consumpting process of early diastolic relaxation, independently of its role as a risk factor for atherosclerosis.

[Multiple proximal coronaro-pulmonary fistulae. Review of the literature apropos of a new case]. / Fistules coronaro-pulmonaires proximales multiples. Revue de la littérature à propos d'un nouveau cas.

The authors report a new case of multiple proximal coronaro-pulmonary fistula between right coronary arteries, anterior interventricular artery and the trunk of the pulmonary artery, in a 64 year-old female patient with chest pain and a continuous murmur located in the third left intercostal space. The coronary steal is demonstrated by a myocardial scintigraphy during stress with return to normal after surgical ligation. A review of the literature enabled to find 33 cases of this major congenital anomaly of the coronary arteries, defined as an abnormal communication between at least two main coronary vessels and the trunk of the pulmonary artery. This results in a left-right shunt, usually minor without any repercussions on the right cavities and pulmonary pressures. The entire clinical, electrocardiographic, radiological, sonographic, scintigraphic, haemodynamic and angiographic picture is reported for these 33 cases. A physiopathological discussion is proposed. The course of this disease is usually favorable (only one case of myocardial infarction was published, without cardiac failure. Osler's endocarditis or sudden death); this seems to authorize simple monitoring as a logical therapeutic approach except when a myocardial ischemia secondary to coronary steal is demonstrated, imposing a surgical correction.

Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II).

AIMS: Numerous markers have been identified as useful predictors of major adverse cardiac events (MACE) in patients with suspected acute coronary syndrome (ACS). However, only little is known about the relative benefit of the single markers in risk stratification and the best combination for optimising prognostic power. The aim of the present study was to define the role of the emerging cardiovascular risk marker lipoprotein-associated phospholipase A2 (Lp-PLA2) in a multi-marker approach in combination with troponin I (TnI), NT-proBNP, high sensitivity (hs)CRP, and D-dimer in patients with ACS. METHODS AND RESULTS: A total of 429 consecutive patients (age 60.5+/-14.1 years, 60.6% male) who were admitted to the emergency room with suspected ACS were analysed in the study. Biochemical markers were measured by immunoassay techniques. All patients underwent point-of-care TnI testing and early coronary angiography if appropriate, in accordance with the current guidelines. Classification and regression trees (CART) and logistic regression techniques were employed to determine the relative predictive power of markers for the primary end-point defined as any of the following events within 42 days after admission: death, non-fatal myocardial infarction, unstable AP requiring admission, admission for decompensated heart failure or shock, percutaneous coronary intervention, coronary artery bypass grafting, life threatening arrhythmias or resuscitation. The incidence of the primary end-point was 13.1%, suggesting a mild to moderate risk population. The best overall risk stratification was obtained using NT-proBNP at a cut-off of 5000 pg/mL (incidence of 40% versus 10.3%, relative risk (RR) 3.9 (95% CI 2.4-6.3)). In the remaining lower risk group with an incidence of 10.3%, further separation was performed using TnI (cut-off 0.14 microg/L; RR=3.1 (95% CI 1.7-5.5) 23.2% versus 7.5%) and again NT-proBNP (at a cut-off of 140 ng/L) in patients with negative TnI (RR=3.2 (95% CI 1.3-7.9), 11.7% versus 3.6%). A final significant stratification in patients with moderately elevated NT-proBNP levels was achieved using Lp-PLA2 at a cut-off of 210 microg/L) (17.9% versus 6.9%; RR=2.6 (95% CI 1.1-6.6)). None of the clinical or ECG variables of the TIMI (Thrombolysis In Myocardial Infarction) risk score provided comparable clinically relevant information for risk stratification. CONCLUSIONS: In the setting of stateof- the-art coronary care for patients with suspected ACS in the emergency room, NT-proBNP, troponin I, and Lp-PLA2 are effective independent markers for risk stratification that proved to be superior to the TIMI risk score. Lp-PLA2 turned out to be a more effective risk marker than hsCRP in these patients.

Left ventricular hypertrophy regression during antihypertensive treatment.

For more than 20 years hypertrophy regression has been in the focus of hypertension research. Many studies in animals have shown impressive reduction of left ventricular hypertrophy after medical treatment of hypertension. The most important result seems to be that hypertrophy can be almost completely reversed in young animals, whereas in older animals regression of left ventricular hypertrophy appears to be less complete. Hypertrophy regression in man seems much more difficult to prove. The direct correlation between left ventricular muscle mass and ECG changes has been disappointing in many studies. Echocardiography is able to show a comparatively good impression of left ventricular muscle mass and therefore can also demonstrate regression of left ventricular hypertrophy within its methodological limits. There is no doubt that today magnetic resonance imaging has by far the best imaging quality of all the clinical methods and is able to demonstrate both hypertrophy and its regression with incomparable accuracy. In the present clinical study hypertrophy regression has been demonstrated after 6 months of treatment with Carvedilol.

[Non-invasive detection of left ventricular diastolic function in variously trained endurance athletes during a marathon run with pulsed Doppler sonography]. / Nichtinvasive Erfassung der linksventrikulären diastolischen Funktion bei unterschiedlich trainierten Ausdauersportlern während eines Marathonlaufs mittels gepulster Doppler-Sonographie.

UNLABELLED: To evaluate left ventricular (LV) diastolic function in long distance runners LV filling parameters were assessed by Doppler echocardiography during marathon race in 23 male subjects. On the basis of their personal record the athletes were divided into two groups: 12 endurance athletes (END; 218 min over 42 km) aged 34 years (29/37, median and 25%/75%-percentiles) and 11 ultra endurance athletes (ULTRA; 152 min over 42 km) aged 32 years (28/37). At rest 21 healthy untrained subjects (UT) aged 33 years (28/37) served as control group. In long distance runners the values for LV mass and LV mass index were significantly higher in END with 210 (168/253) g rsp. 110 (87/135) g/m2 and in ULTRA with 225 (179/267) g rsp. 118 (93/142) g/m2 as compared to UT with 129 (105/162) g rsp. 68 (57/79) g/m2 (p less than 0.001 each). Doppler-derived mitral flow was characterized by the early passive (E wave) and late (A wave) diastolic inflow. In particular atrial filling fraction (AFF) as the relative atrial contribution to LV filling was measured. At rest and at km 21 we saw a normal filling behaviour (AFF = 27% bzw. 28%) in both groups of long distance runners with an AFF of 27 (26/29)% in END and an AFF of 28 (26/29) in ULTRA. In END AFF rose to 42 (38/47)% at km 42 (p less than 0.001) and remained significantly elevated with 37 (35/42)% until 30 min post marathon (p less than 0.05). Only 60 min post exercise AFF returned to baseline values with an AFF of 28 (25/39)% in END. In contrast at km 42 in ULTRA AFF was significantly lower and at baseline levels with 26 (25/29)% compared to END (p less than 0.001) and did not significantly change in the further course of the post running period. CONCLUSION: Long distance runners show a normal LV filling behaviour at rest despite significant LV hypertrophy. In contrast to top class athletes (ULTRA) there is a shift of LV filling from early (E wave) to late (A wave) diastole in less trained runners (END) during marathon. Thus, the results indicate an impairment of early diastolic LV filling in amateur endurance athletes (END) during extreme physical exercise.

[Possibilities for imaging intracardiac thrombi with indium 111 thrombocyte scintigraphy]. / Darstellungsmöglichkeit intrakardialer Thromben durch die Indium-111-Thrombozytenszintigraphie.

Intracardiac thrombi can be localized and quantified by indium-111-labelling of thrombocytes with a high sensitivity and specificity. The scintigraphic procedure has a complementary evidence to echocardiography. Scintigraphy shows activity and age of thrombosis, whereas echocardiography seems to be superior in determination of mass and localization. In older thrombi scintigraphy fails because of organisation and endothelialization of the thrombus surface. For the reason of determination of the age of an intraventricular thrombus this method might have an increasing acceptance.

[Imaging of intra-cardiac thrombi with indium 111 scintigraphy]. / Darstellbarkeit intrakardialer Thromben durch die Indium-111-Szintigraphie.

Intracardiac thrombi can be localized and quantified by Indium-111-labelling of thrombocytes with a high sensitivity and specificity. The scintigraphic procedure has a complementary evidence to echocardiography. Scintigraphy shows activity and age of thrombosis, whereas echocardiography seems to be superior in determination of mass and localization. In older thrombi scintigraphy fails because of organisation and endothelialization of the thrombus surface. For the reason of determination of the age of an intraventricular thrombus this method might have an increasing acceptance.

Regression of left ventricular hypertrophy under ramipril treatment investigated by nuclear magnetic resonance imaging.

Thirty-two hypertensive subjects with diastolic blood pressure greater than 95 mm Hg were treated with ramipril over a period of 3 months. To determine the effective decrease of blood pressure and for reliable and reproducible demonstration of regression of myocardial hypertrophy during ramipril treatment, we performed parallel measurements with magnetic resonance imaging (MRI) and echocardiography. Measurements were carried out before treatment, 4 h after the first dose, and after 14 days and 3 months of treatment. MRI slices showed a significant decrease of interventricular septal thickness from 19.57 to 15.20 mm, whereas echocardiography demonstrated an equivalent decrease from 18.78 to 14.57 mm. At each measuring point, quantification of wall thickness was performed three times and the means were calculated. The septum and the posterior wall of the left ventricle were also measured at three different points. The values were obtained with negligible scatter and the changes with ramipril treatment were highly significant (p less than 0.001). A concomitant decrease of blood pressure was also observed. The therapeutic aim to reduce diastolic blood pressures below 90 mm Hg was achieved in all patients. In addition to the significant reduction in blood pressure, the angiotensin converting enzyme (ACE) inhibitor ramipril caused a significant regression of pathologic left ventricular hypertrophy demonstrated by magnetic resonance imaging and echocardiography.

Imaging of acute myocardial infarction by magnetic resonance tomography (MRT) using the paramagnetic relaxation substance gadolinium-DTPA.

Twenty-six patients admitted to the Free University of Berlin University Hospital catheterization laboratory with acute myocardial infarction were studied. The diagnosis was confirmed by angiography, but acute revascularization was unsuccessful in every case. MR imaging was performed within 7 days of the acute event in 11 patients with uncomplicated clinical courses after acute infarction. Imaging was performed within 3 weeks in three additional cases, while the remaining 12 patients underwent studies more than 3 weeks after infarction. We determined signal intensity at three points within the area of infarction and at three other points in adjacent myocardial tissue. Decreased signal intensity within the area of infarction was found in native scans in 60% of all cases. Administration of gadolinium-DTPA 0.1 mmol/kg body weight was followed by a mean 70% increase in signal intensity within the zones of acute infarction, as compared to a 20% increase in surrounding myocardial tissue. In cases of subacute and chronic infarction, there was no significant signal enhancement after administration of gadolinium-DTPA. Uptake of the substance in the area of acute infarction may be a positive marker of acute myocardial necrosis and as such may prove useful in the clinical setting.

Microperfusion in coronary artery disease under treatment with the calcium antagonist gallopamil.

The calcium antagonistic principle, i.e. the inhibition of calcium influx into the heart muscle cell and smooth muscle cell, in this particular case gallopamil as an example of a drug with this principle of action, can certainly be regarded as one of the most important concepts in modern coronary therapy. On account of the increase of myocardial perfusion, which is ascribed to this calcium antagonist, gallopamil may be administered as an adjunct to postoperative therapy. It is even a drug alternative to bypass grafting. Previous investigations of the ST segment and subjective ischemic parameters have not always shown coherent findings. The purpose of this study was to objectify clinical improvement after therapy with gallopamil (Procorum) by means of reliable methods and reproducible measurements. Myocardial perfusion was analysed in 31 patients by longitudinal tomoscintigraphy before and after therapy with 2 x 2 mg gallopamil intravenously and 6 weeks at 3 x 50 mg/d orally followed by placebo control. The computerized circumferential mapping of impulse rates showed a significant increase of impulse density in ischemic segments after both intravenous and oral therapy with gallopamil.