An aim of modern medicine is to provide personalized or individualized treatment regimens. Those are treatment regimens which take into account a patient's individual needs or risks. Personalized or individual treatment regimens shall be even taken into account for emergency measures where it is required to decide on potential treatment regimens within short periods of time. Heart diseases are the leading cause of morbidity and mortality in the Western hemisphere. The diseases can remain asymptomatic for long periods of time. However, they may have severe consequences once an acute cardiovascular event, such as myocardial infarction, as a cause of the cardiovascular disease occurs.
Heart failure is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. Even with the best therapy, heart failure is associated with an annual mortality of about 10%. Heart failure is a chronic disease; it can, inter alia, occur either following an acute cardiovascular event (like myocardial infarction), or it can occur, e.g., as a consequence of inflammatory or degenerative changes in myocardial tissue. Heart failure patients are classified according to the NYHA system in classes I, II, III and IV. A patient having heart failure will not be able to fully restore his health without receiving a therapeutic treatment.
Myocardial dysfunction is a general term, describing several pathological states of the heart muscle (myocard). A myocardial dysfunction may be a temporary pathological state (caused by, e.g., ischemia, toxic substances, and alcohol), contrary to heart failure. Myocardial dysfunction may disappear after removing the underlying cause. A symptomless myocardial dysfunction may, however, also develop into heart failure (which has to be treated in a therapy). A myocardial dysfunction may, however, also be a heart failure, a chronic heart failure, even a severe chronic heart failure.
Myocardial dysfunction and heart failure often remain undiagnosed, particularly when the condition is considered “mild.” The conventional diagnostic techniques for heart failure are based on the well known vascular volume stress marker NT-proBNP, a natriuretic peptide. However, the diagnosis of heart failure under some medical circumstances based on NT-proBNP appears to be incorrect for a significant number of patients but not all (e.g., Beck 2004, Canadian Journal of Cardiology 20: 1245-1248; Tsuchida 2004, Journal of Cardiology, 44:1-11). However, especially patients which suffer from heart failure would urgently need a supportive therapy of the heart failure. On the other hand, as a consequence of an incorrect diagnosis of heart failure, many patients will receive a treatment regimen which is insufficient or which may have even adverse side effects.
Patients having heart failure may also develop an acute cardiac disorder, in general an acute coronary syndrome. ACS covers the states of unstable angina pectoris UAP and acute myocardial infarction MI.
MI is classified as belonging to coronary heart diseases CHD and is preceded by other events also classified as belonging to CHD, like unstable angina pectoris UAP. Symptomatic for UAP is chest pain which is relieved by sublingual administration of nitroglycerine. UAP is caused by a partial occlusion of the coronary vessels leading to hypoxemia and myocardial ischemia. In case the occlusion is too severe or total, a myocardial necrosis (which is the pathological state underlying myocardial infarction) results. MI may occur without obvious symptoms, i.e., the subject does not show any discomfort, and the MI is not preceded by stable or unstable angina pectoris.
UAP, however, is a symptomatic event preceding MI. A CHD in a subject may also occur symptomless, i.e., the subject may not feel uncomfortable and exhibit any signs of CHD like shortness of breath, chest pain or others known to the person skilled in the art. The subject, however, may be pathological and suffer from a malfunction of his coronary vessels which may result in a MI and/or congestive heart failure CHF, meaning the heart does not have the capacity to perform as required in order to ensure the necessary provision of blood to the subject's body. This may result in severe complications, one example of which is cardiac death.
Patients suffering from symptoms of an acute cardiovascular event (e.g., myocardial infarction) such as chest pain are currently subjected to a cardiac troponin based diagnosis, generally troponin T or troponin I. To this end, troponin T/I levels of the patients are determined. If the amount of troponin T in the blood is elevated, i.e., above 0.1 ng/ml, an acute cardiovascular event is assumed and the patent is treated accordingly.
However, by exclusively measuring natriuretic peptides, the information obtained does not allow to assess if a myocardial dysfunction already existed prior to the acute myocardial infarction.
An acute myocardial infarction is caused by an occlusion of a heart coronary vessel, resulting in the death of a region of various size of the heart muscle tissue. The death of the myocard causes an elevation of troponin T (a heart-specific molecule) or troponin I, which can be detected in serum/plasma. Furthermore, the death of the myocard is connected with a loss of the pump function of the heart, resulting in an elevated level of natriuretic peptides.
The level of troponin T- and also troponin I- and the natriuretic peptides, in particular NT-proBNP, starts to raise about 4-6 hours after a myocardial infarction. Patients consulting their physician after that time, have an elevated level of the peptides.
With respect to the value of the natriuretic peptides, in particular NT-proBNP, it cannot be assessed if                a) the elevated level of the peptide is a consequence of the acute MI, or if        b) the elevated NT-proBNP value already existed prior to the MI, or if        c) the value is caused by both the degeneration of the cardial function by the MI and the pre-existing myocardial dysfunction. It would be desirable to have means and methods permitting to differentiate between the topics laid out beforehand.        
The technical problem underlying the present invention can be seen as the provision of means and methods for complying with the aforementioned needs. The technical problem is solved by the embodiments characterized in the claims and herein below.