Johannes Mair

Metapress is a fast growing digital platform that helps visitors to answer questions, solve problems, learn new skills and find inspiration. With detailed business advice, website tips, marketing resources, detailed research, dynamic tools and honest reviews – We're on a mission to...

The recent guidelines of the European Society of Cardiology, recommends laboratory testing as an essential part of the evaluation of the patient presenting with acute or chronic heart failure. The decrease in BNP has been included as a treatment goal for the management of acute heart failure. As for other properties it is important to define what difference can be considered as a real change of the marker in serial measurements. Therefore, knowledge of pathophysiological influences and pre‐analytical issues as well as the intraindividual variability of BNP and N‐terminal proBNP (NT‐proBNP) due to analytical imprecision and biological variation is crucial. Erroneous test results with BNP or NT‐proBNP assays are rare but may occasionally occur analytical interferences and should be suspected if the results do not suit the clinical picture or the serial kinetics. Although BNP assays correlate closely, due to lack of standardization no two BNP assays are analytically equivalent, and the same assay must be used for serial measurement. The in‐vitro stabilities of BNP and NT‐proBNP are sufficient for routine use, and blood sampling for BNP or NT‐proBNP directly after arrival without a standardized period of rest is feasible, however, heavy physical exercise should be avoided before blood sampling. To be on the safe side a period of 10 minutes rest before blood sampling is recommended. BNP and NT‐proBNP are suitable for heart failure monitoring, and BNP and NT‐proBNP changes >50% from baseline correlated well with clinical course and a reduction of mortality in heart failure patients.

The long-predicted natriuretic and endocrine function of the heart was demonstrated more than 20 years ago ( 1) by the discovery of atrial natriuretic peptide [atrial natriuretic factor, A-type natriuretic peptide (ANP)]. This led to the description of a family of structurally similar but genetically distinct peptides, constituting the natriuretic peptide (NP) family, which contribute to the maintenance of cardiovascular homeostasis. These looped peptides are the naturally occurring antagonists of the renin-angiotensin-aldosterone system and of the sympathetic nervous system. They promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues.

The long-predicted endocrine function of the heart has been proven by the discovery of atrial natriuretic peptide (atrial natriuretic factor, A-type natriuretic peptide; ANP) 20 years ago. This subsequently led to the description of a whole family of structurally similar but genetically distinct peptides, the natriuretic peptide family, which contributes to cardiovascular homeostasis. These looped peptides promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues. Two members, ANP and brain natriuretic peptide (B-type natriuretic peptide; BNP) are secreted by the heart mainly in response to myocardial stretch induced by volume load. The natriuretic peptides are synthesized as preprohormones. The C-terminal endocrinological active peptides (ANP, BNP) and their N-terminal prohormone fragments are found in plasma. The natriuretic peptide system is activated to its highest degree in ventricular dysfunction. However, natriuretic peptides are increased in all patients with edematous disorders which lead to an increase in atrial tension or central blood volume, such as renal failure or ascitic liver cirrhosis. It could be demonstrated that in chronic heart failure patients and during the subacute phase of myocardial infarction, of all tested neurohormones, the cardiac natriuretic peptides were best markers to identify heart failure and the most powerful predictors of morbidity and mortality. Natriuretic peptides are independent markers for risk assessment. In comparative studies BNP was superior to ANP and its N-terminal prohormone fragments in myocardial infarction as well as in chronic heart failure patients. Less data on N-terminal proBNP (NT-proBNP) is available, but BNP and NT-proBNP appear to be equivalent markers. For primary care physicians natriuretic peptide measurement is useful to decide which patient with suspected heart failure warrants further investigation, particularly when assessment of left ventricular function is not readily available. Natriuretic peptides have an excellent negative predictive value, particularly in high risk patients. An increase in BNP is serious enough to warrant follow-up examinations. For the cardiologists the natriuretic peptides are helpful for guidance of therapy and monitoring disease course in heart failure patients and for risk stratification in heart failure and myocardial infarction.

The early release of cardiac markers is influenced by a variety of factors, the most important influence being their intracellular compartmentation. In contrast to the release of cytosolic proteins, the release of structurally bound proteins requires both a leaky plasma membrane and a dissociation or degradation of the subcellular structure, which is a slower process. Another major impact is the susceptibility to the degradation by cytosolic proteases, such as the calpains. The lysosomes are stable within the first 3–4 hours after onset of ischemia, and, therefore, their enzymes are not involved in the early degradation of structurally bound proteins. Troponin I and troponin T are substrates of μ-calpain. Current experimental as well as clinical results suggest that the molecular mass seems to be of minor importance for the pattern of appearance of myocardial proteins in blood after myocardial infarction. However, within the family of molecules with a certain intracellular compartmentation, the molecular mass is an influence on the appearance in blood, because heavier molecules diffuse at a slower rate, and particularly smaller molecules, such as myoglobin, may enter the vascular system to an even larger extent directlyviathe microvascular endothelium. The higher the concentration gradient of a marker between the cardiomyocytes and the interstitial space, the faster a parameter will translocate from sarcoplasma to the interstitial space as soon as the plasma membrane permeability is increased. Another influence is local blood and lymphatic flow. Recent experimental studies showed that reperfusion causes a true acceleration of cellular protein leakage by an acute manifestation of plasmalemmal disruptions and not just an enhanced wash out. Marker protein time-courses after myocardial damage are also markedly influenced by their disappearance rate from blood. Most proteins appear to be catabolized in organs with a high metabolic rate, such as liver, pancreas, kidneys, and the reticuloendothelial system. Smaller molecules, such as myoglobin, also pass the glomerular membranes of the kidneys and are reabsorbed and subsequently metabolized in tubular epithelial cells.

We investigated the net myocardial release of creatine kinase isoenzyme MB (CKMB), myoglobin, cardiac troponin T (cTnT), cardiac troponin I (cTnI), and cardiac β-type myosin heavy chain (β-MHC) into the coronary circulation after cardioplegic cardiac arrest in humans. Cardiac markers were measured in paired arterial, central venous, and coronary sinus blood in 19 patients undergoing elective coronary artery bypass grafting (CABG) before aortic cross-clamping and 1, 5, 10, and 20 min after aortic declamping. cTnT and cTnI were released into the coronary sinus in parallel to each other and almost simultaneously to myoglobin and CKMB within 20 min of reperfusion. In contrast, no β-MHC was released in the same patients during the study period. The average soluble cTnT and cTnI pools in right atrial appendages of 11 patients with right atrial and right ventricular pressures within reference values were comparable and were ∼8% of total myocardial troponin content. The soluble β-MHC pool was <0.1% in all patients. Our results demonstrate the impact of the different intracellular compartmention of regulatory and contractile proteins on their early release from damaged myocardium.

Plasma concentrations of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and D-dimer were investigated in 50 patients treated intravenously for acute myocardial infarction with either streptokinase (n = 23), urokinase (n = 17), or recombinant t-PA (rt-PA, n = 10). The fibrinolytic variables were measured by enzyme immunoassay on admission; 1, 2, 4, 6, 8, 12, and 24 h later; and then daily until day 7 after admission. In each subgroup of patients treated with different thrombolytic agents, PAI-1 increased significantly (P 0.14) among subgroups except for higher t-PA in the rt-PA group attributable to detection of the therapeutically administered exogenous rt-PA by the t-PA assay. Our findings demonstrate a marked PAI-1 increase after thrombolytic therapy for acute myocardial infarction, which seems to be a common, drug-independent antifibrinolytic rebound phenomenon in response to thrombolytic treatment.