Zytokine bei Herzerkrankungen

Die Erforschung der Pathogenese von Herzerkrankungen hat in den letzten Jahren eine neue Richtung bekommen. Zunehmend treten inflammatorische Komponenten sowohl als prognostische Marker als auch als Mitverursacher beispielsweise der chronischen Herzinsuffizienz in die Diskussion. Der vorliegende Beitrag gibt einen überblick über neue Erkenntnisse m?glicher Pathomechanismen in Folge sowohl kardialer als auch extrakardialer Zytokinwirkungen. Diese neue Konzept kann in Zukunft neue therapeutische Strategien zur Verbesserung der noch immer schlechten Prognose der chronischen Herzinsuffizienz er?ffnen.     

Zytokine bei Herzerkrankungen

Zum Thema Die Erforschung der Pathogenese von Herzerkrankungen hat in den letzten Jahren eine neue Richtung bekommen. Zunehmend treten inflammatorische Komponenten sowohl als prognostische Marker als auch als Mitverursacher beispielsweise der chronischen Herzinsuffizienz in die Diskussion. Der vorliegende Beitrag gibt einen überblick über neue Erkenntnisse m?glicher Pathomechanismen in Folge sowohl kardialer als auch extrakardialer Zytokinwirkungen. Diese neue Konzept kann in Zukunft neue therapeutische Strategien zur Verbesserung der noch immer schlechten Prognose der chronischen Herzinsuffizienz er?ffnen.     

Antikoagulation bei Herzinsuffizienz

Zum Thema Das thromboembolische Risiko von Patienten mit Herzinsuffizienz aufgrund chronischer linksventrikul?rer Dysfunktion ist erh?ht. Bei der Indikationsstellung zu einer oralen Dauerantikoagulation mu? das Thromboembolierisko gegenüber den m?glichen Blutungskomplikationen einer solchen Therapie abgewogen werden. Da es keine prospektive kontrollierte Studie gibt, die den Effekt einer oralen Dauerantikoagulation bei Patienten mit Herzinsuffizienz aufgrund chronischer linksventrikul?rer Dysfunktion untersucht h?tte, wird die Indikation zur Antikoagulation bei diesen Patienten kontrovers diskutiert und unterschiedlich gehandhabt. Die folgende übersicht gibt den heutigen Kenntnisstand wider und leitet daraus Empfehlungen für eine orale Antikoagulation bei Patienten mit Herzinsuffizienz und/oder chronischer linksventrikul?rer Dysfunktion ab.     

Antikoagulation bei Vorhofflimmern

Atrial fibrillation is the most common arrhythmia in the elderly and is associated with substantial morbidity and mortality, mostly due to the consequences of thromboembolism. Anticoagulation reduces the risk of stroke and death considerably, the risk reduction depending on the patient's absolute risk. Although there is modest benefit from acetylsalicylic acid, randomized trials have shown that it is consistently and substantially less effective than vitamin K antagonists. These benefits must be balanced against an increased risk of bleeding. In addition, warfarin therapy imposes a variety of lifestyle constraints, including frequent blood test monitoring and, possibly, dietary modification, and is associated with a number of drug interactions. Careful assessment of the absolute risk of stroke on the one hand and bleeding complications on the other hand will guide the use of appropriate prophylaxis against thromboembolism and its consequences.     

Schwangerschaftsrisiken bei erworbenen Herzerkrankungen

Summary Optimal management of pregnancies for patients with acquired heart disease requires exact knowledge of the hemodynamic influence of pregnancy-related cardiovascular adaptation processes on the heart disease. Maternal and fetal risks must be carefully considered and mutually weighed. Critical time periods, during which closely networked, interdisciplinary support for the patient is essential, are primarily during the 30th to 32nd week of pregnancy. This is the period in which maximum increases in heart rate, cardiac output, and plasma volume are observed. The peripartal phase represents another critical period. Owing to the mechanically related fixation of cardiac output, stenotic valvular diseases are generally tolerated much poorer than are valvular insufficiency defects. Therapeutic objectives are reduction in heart rate and - in cases of pulmonary-venous congestion - decrease in preload. Vaginal deliveries are possible with slight to moderate valvular stenosis; cesarean section is to be preferred in more severe cases. In patients with valvular insufficiency and normal left ventricular function pregnancy is usually well tolerated. Reduction in regurgitation is even often observed owing to pregnancy-induced decrease in peripheral vascular resistance. Since ACE inhibitors and AT₁ antagonists are contraindicated during pregnancy, afterload reduction can be achieved by a combination of hydralazin and nitrates, or calcium antagonists. Peripartal cardiomyopathy is rare and is associated with a high degree of maternal mortality (25 - 50 %). Apart from the necessary consideration of pregnancy-related contraindications, therapeutic principles do not differ from those for other forms of heart failure. Most patients exhibiting hypertrophic obstructive cardiomyopathy satisfactorily pass through their pregnancies. Individual cases have been described, however, of both pregnancy-related cardiac decompensation as well as sudden death. Aortal and coronary-arterial dissections represent rare, life-endangering complications for mother and fetus: these developments can occur among predisposed patients as a result of the hormonal and hemodynamic adaptation processes during pregnancy. Close interdisciplinary collaboration and tightly networked support for patients are the prerequisite for successful management of high-risk pregnancies involving maternal heart disease. Zusammenfassung Optimales Management von Schwangerschaften bei Patientinnen mit erworbenen Herzklappenfehlern setzt genaue Kenntnis der hämodynamischen Auswirkungen des Vitiums auf die schwangerschaftsbedingten kardiovaskulären Adaptationsvorgänge voraus. Mütterliches und fätales Risiko sind in Betracht zu ziehen und gegeneinander abzuwägen. Kritische Zeitpunkte, in denen die Patientinnen interdisziplinär engmaschig betreut werden sollten, sind v.a. die 30. - 32. Schwangerschaftswoche, in der ein maximaler Anstieg von Herzfrequenz, Herzzeitvolumen (HZV) und Plasmavolumen beobachtet wird, sowie die peripartale Phase. Stenosevitien werden generell durch die mechanisch bedingte Fixierung des HZV deutlich schlechter toleriert als Insuffizienzvitien. Therapeutische Ziele sind Senkung der Herzfrequenz und, bei pulmonalvenöser Kongestion, die Vorlastsenkung. Vaginale Entbindungen sind bei leicht- bis mittelgradigen Stenosevitien möglich, bei höherem Schweregrad ist eine Sectio caesarea vorzuziehen. Insuffizienzvitien werden bei normaler Pumpfunktion besser toleriert. Oft wird sogar durch den schwangerschaftsinduzierten Abfall des periphären Widerstandes eine Reduktion der Regurgitation beobachtet. Therapeutisch kann eine zusätzliche Nachlastsenkung bei Kontraindikationen gegen ACE-Hemmer und AT1-Antagonisten durch eine Kombinationstherapie aus Hydralazin und Nitraten oder Kalziumantagonisten erzielt werden. Peripartale Kardiomyopathien sind selten und mit einer hohen mütterlichen Mortalität von 25 - 50 % assoziiert. Die Therapieprinzipien unterscheiden sich - unter Beachtung der schwangerschaftsbedingten Kontraindikationen - nicht von denen anderer Herzinsuffizienzformen. Schwangerschaften bei hypertropher obstruktiver Kardiomyopathie werden meist gut überstanden, allerdings sind sowohl vereinzelte schwangerschaftsassoziierte Dekompensationen als auch plötzliche rhythmogene Todesfälle beschrieben worden. Seltene, lebensbedrohliche Komplikationen für Mutter und Fötus stellen aortale oder koronararterielle Dissektionen dar, die bei prädisponierten Patientinnen durch hormonelle und hämodynamische Adaptationsvorgänge in der Schwangerschaft auftreten können. Grundvoraussetzung für ein erfolgreiches Management einer Risikoschwangerschaft bei maternaler Herzerkrankung ist eine enge interdisziplinäre Zusammenarbeit und die engmaschige Betreuung der Patientinnen.     

Antikoagulation bei Niereninsuffizienz

The prevalence and incidence of chronic kidney disease has increased continuously in Europe and the USA over the last decades. Renal failure also is one of the main complications in critically ill patients. The high frequency of chronic kidney disease, the high cardiovascular comorbidity and the use of extracorporal renal replacement therapies increase the need for anticoagulation tailored to the needs of the individual patient and to the special clinical circumstances. Unfractionated heparins (UFH) and their derivates, the low molecular weight heparins (LMH) and heparinoids, are among the most frequently used parenteral anticoagulants. New direct thrombin inhibitors (DTI) with different pharmacokinetics are appearing, offering interesting options as alternative anticoagulants. This article reviews the pharmacology and the clinical applications of the most common parenteral anticoagulants with a focus on renal failure.     

Antikoagulation bei Vorhofflimmern

According to new criteria based on the CHAD(2)DS(2)-VASc score, the threshold for administering anticoagulation therapy for atrial fibrillation patients is being increasingly lowered. With the development of new anticoagulants, more therapy options are available. Currently, vitamin K antagonists are still the standard treatment. However, this therapy is problematic for some patients. Because of the increased bleeding risk and need for continuous blood tests to monitor coagulation, many patients needing anticoagulation therapy are not treated. The new anticoagulants apixaban, rivaroxaban and dabigatran were developed with the goal of avoiding these problems. Dabigatran has already been approved for thromboembolism prophylaxis for patients with atrial fibrillation. All three substances do not require routine control blood tests. Whether the costs saved by this together with the prevention of ischemic and bleeding events justify the higher price of these drugs compared to vitamin K antagonists needs to be examined by socioeconomic studies.     

Antikoagulation bei Vorhofflimmern

Atrial fibrillation is associated with a relevant risk for ischemic stroke: Observational studies suggest that one in four to five strokes is due to atrial fibrillation. Depending on the risk profile of an individual patient, the yearly risk for a stroke is between 2% and 14%. Continuous oral anticoagulation is indicated if atrial fibrillation is accompanied by at least one additional risk factor for thromboembolic complications. This recommendation is supported by several large randomized trials. Due to their low therapeutic range, vitamin K antagonists (phenprocoumon, warfarin, and others), the most commonly used oral anticoagulants, require regular anticoagulation monitoring. If well-controlled (international normalized ratio 2-3, in elderly patients preferably 2-2.5), oral anticoagulation prevents more than half of ischemic strokes related to atrial fibrillation, while bleeding complications are rare. In the follow-up of low risk patients (CHADS2-Score 0), oral anticoagulation becomes necessary when risk factors for thromboembolic complications develop. If a stroke occurs during oral anticoagulation and an INR>2 in a patient with atrial fibrillation, other causes than thromboembolic events should be considered. New anticoagulants--especially direct thrombin antagonists--are currently evaluated in clinical trials and may in the future facilitate anticoagulation in patients with atrial fibrillation.     

Antikoagulation bei Diabetes mellitus

Patients with diabetes mellitus have an increased cardiovascular risk (annual risk of coronary heart disease >1.5%), and in the case of a cardiovascular event, their prognosis is worse than that of nondiabetic patients. Medication with 100 mg aspirin is indicated following a cardiovascular event (stroke, myocardial infarction) for secondary prevention, as it reduces mortality, and because of diabetics’ high risk, this dose is also recommended for primary prevention. Following coronary stent implantation, dual antiplatelet therapy with 100 mg aspirin and 75 mg clopidogrel should be initiated. Dual antiplatelet therapy should be given for 4 weeks if a bare metal stent was used and should be prolonged to a minimum of 6 months (even better, 12 months) following implantation of a drug-eluting stent. Oral anticoagulation does not differ in diabetics and nondiabetics if proliferative diabetic retinopathy can be ruled out.     

Orale Antikoagulation bei Herzinsuffizienz

The risk of thromboembolic complications is increased in patients with advanced chronic heart failure and severe left ventricular dysfunction. Accepted indications for oral anticoagulation include patients with a history of thromboembolism, concomitant atrial fibrillation, or venous, arterial or cardiac thrombosis. In other subgroups, the benefit of chronic anticoagulation has not been proven and existing data from uncontrolled nonrandomized, mostly retrospective studies and prospective, randomized controlled studies are conflicting.This article summarizes the available data on the thromboembolic risk and the potential benefit of antithrombotic therapy and attempts to provide current orientation and recommendations for anticoagulant therapy in patients with chronic heart failure and severe left ventricular dysfunction.     

Orale Antikoagulation bei Vorhofflimmern

The correct oral anticoagulation for prevention of thromboembolic events in patients with atrial fibrillation and a corresponding risk profile is essential. However, anticoagulation is not carried out according to the guidelines in all patients. The direct oral anticoagulants (DOACs) are a new treatment alternative to vitamin K antagonists. The new guidelines of the European Society of Cardiology (ESC), recent study results and the practice guidelines of the European Heart Rhythm Association (EHRA) can help to use DOACs appropriately, to optimize the prevention of thromboembolic events in patients with atrial fibrillation and to reduce complications.     

Insulintherapie bei Patienten mit Herzerkrankungen

Insulin therapy in patients with heart failure and coronary artery disease is controversially discussed. While early short-term interventions after a myocardial event seem to exert a positive influence on the later mortality rate, long-term cohort studies have not been able to confirm any positive effect of insulin in comparison to other anti-diabetic strategies. However, in these studies insulin was given at a very late stage of the disease to multimorbid patient populations and it is not possible to extract the individual effects of insulin on the prognosis in a clear way. There are indications that negative outcome with insulin therapy may be related to the degree of endothelial insulin resistance. Short-term interventions with insulin in combination with insulin sensitizers have already shown indications of an improved vascular condition. However, further confirmatory long-term studies are necessary before any practical recommendations can be given in this respect to practicing physicians.     

Herzerkrankungen bei Tumoren und Tumortherapie

Cardiac disease may occur as a direct complication of heart tumors or as an indirect complication of malignancies due to antineoplastic therapy. While primary cardiac neoplasias are rare, metastases to various cardiac structures are common. The cardiotoxicity of anticancer agents can lead to significant complications that may affect patients being treated for various non-cardiac neoplasias. The severity of such cardiovascular damage depends on many factors, such as the site of molecular action, the immediate and cumulative dose, the method of administration, and the presence of any underlying cardiac condition. Moreover, toxicity can be affected by concomitant radiation. Cardiotoxic effects can occur during the administration of the drug, but they may not manifest themselves until months or years after the patient has been treated. Since cardiovascular disease and cancer are both common, precise knowledge of therapeutic interactions and complications is necessary.     

Antikoagulation bei pulmonaler arterieller Hypertonie

Pulmonary arterial hypertension (PAH) often affects young patients for whom life-long anticoagulation can represent an incisive decision. Therefore, it is important to analyze the sometimes conflicting clinical and scientific results for this therapy. PAH is often accompanied by thrombosis and thrombo-embolisms in the pulmonary circulation, in particular the small pulmonary arterioles with prothrombotic and reduced antifibrinolytic activity due to endothelial dysfunction. Measurable alterations of coagulation factors are of prognostic significance. Thrombocyte function is also disrupted. Furthermore, most patients with PAH have a right-sided cardiac insufficiency with an enlarged right ventricle and reduced circulation. In addition to these pathophysiologic findings four non-randomized studies, which allow the assumption of improved prognosis by phenprocoumon therapy, have confirmed the rational of anticoagulation for PAH and the recommendations of national and international guidelines. Clinical studies on alternatives, such as the administration of acetylsalicylic acid have not yet been carried out. Efforts should be made to diagnose the disease as early as possible in order to correct alterations in coagulation and thrombocyte function by an early therapy.