Ruschitzka, Frank T.

Abstract There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

Analgetika sind die am häufigsten verschriebenen Medikamente. Neben ihrer analgetischen Wirksamkeit sind diese Arzneimittel mit einem erhöhten kardiovaskulären Risiko assoziiert, das nicht zuletzt auch auf eine durch die Wirksubstanzen selbst bedingte Erhöhung des Blutdrucks zurückzuführen ist. Epidemiologische und klinische Studien zeigten bereits, dass viele nicht-selektive nicht-steroidale-Antirheumatika und selektive Cyclooxygenase-2-Hemmer mit einer Erhöhung des Blutdrucks und einem erhöhten kardiovaskulären Ereignis einhergehen. Leider fehlten bislang Ergebnisse von prospektiven, randomisierten klinischen Studien mit klinisch relevanten Endpunkten, insbesondere bezüglich des möglichen Zusammenhangs zwischen kardiovaskulären Ereignissen und Analgetika zu eruieren. Dieses Review soll einen kurzen Überblick über klinische Daten bezüglich der Wirkung des Analgetikums Paracetamol auf den Blutdruck und die klinische Bedeutung verschaffen.

The cardiovascular system is regulated by hemodynamic and neurohumoral mechanisms. These regulatory systems play a key role in modulating cardiac function, vascular tone, and structure. Although neurohumoral systems are essential in vascular homeostasis, they become maladaptive in disease states such as hypertension, coronary disease, and heart failure. The clinical success of ACE inhibitors has led to efforts to block other humoral systems. Neutral endopeptidase (NEP) is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site. NEP is the major enzymatic pathway for degradation of natriuretic peptides, a secondary enzymatic pathway for degradation of kinins, and adrenomedullin. The natriuretic peptides can be viewed as endogenous inhibitors of the renin angiotensin system. Inhibition of NEP increases levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) of myocardial cell origin, and C-type natriuretic peptide (CNP) of endothelial cell origin as well as bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide and kinin systems, vasopeptidase inhibitors reduce vasoconstriction, enhance vasodilation, improve sodium/water balance, and, in turn, decrease peripheral vascular resistance and blood pressure and improve local blood flow. Within the blood vessel wall, this leads to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and increased local levels of bradykinin (and, in turn, nitric oxide) and natriuretic peptides. Preliminary clinical experiences with vasopeptidase inhibitors are encouraging. Thus, the combined inhibition of ACE and neutral endopeptidase is a new and promising approach to treat patients with hypertension, atherosclerosis, or heart failure.