[Diagnostics and therapy of heart failure]. / Diagnostik und Therapie der Herzinsuffizienz.

Heart failure represents one of the most common diseases in the western world with an estimated prevalence of 0.4-2% in Europe. The frequency and incidence is very age-dependant and chronic cardiac insufficiency has a high stage-dependant mortality. Aging of the population and prolongation of the lives of cardiac patients has led to an increasing prevalence of heart failure. However, average survival remains poor after hospitalization for a first episode of heart failure. Diagnostics and therapy of heart failure are subject to constant change due to ongoing progress in research and new randomized controlled trials. This review will focus on new developments and current guidelines for diagnosis and treatment of heart failure. Findings on natriuretic peptides and echocardiography in patients with preserved ejection fraction will be presented and innovative therapeutic measures, such as ivabradine will be discussed. Besides new drug developments insight into device therapy, such as MitraClip® and operative approaches for heart failure will be presented.

[New tyrosine kinase and EGFR inhibitors in cancer therapy. Cardiac and skin toxicity as relevant side effects. Part A: heart]. / Neue Tyrosinkinase- und EGFR-Inhibitoren in der Tumortherapie. Herz und Haut als wichtige Schädigungsorgane. Teil A: Herz.

Cardiotoxicity is a serious side effect of targeted molecular therapies in cancer treatment. Monoclonal antibodies and tyrosine kinase inhibitors are known to be potent therapies in various neoplastic diseases due to inhibition of specific signal transduction pathways. Although targeted therapies are considered to be less toxic and better tolerated than common chemotherapies certain cardiac side effects have been observed. Cardiac toxicity may range from asymptomatic reduction of left ventricular function to life-threatening events like heart failure and acute coronary syndrome. Further side effects are arterial hypertension, thrombosis and arrhythmias. Cardiovascular side effects are common for anti-HER2 therapy in combination with anthracyclines and for inhibitors of angiogenesis. In these patients careful cardiac monitoring is warranted. Because of missing randomized long-term follow-ups, information about cardiac side effects is limited in newly developed targeted molecular therapies. In case of cardiac side effects or preexisting cardiac disease before therapy initiation, assessments by a cardiologist throughout the course of treatment are important. For patients with severe cardiac side effects, discontinuation of treatment is warranted; in case of asymptomatic cardiac side effects symptom-specific therapy should be performed.

[Cryothermal energy: a new perspective for interventional therapy of cardiac arrhythmias?]. / Cryothermie: Eine neue Perspektive in der interventionellen Therapie von Herzrhythmusstörungen?

Cryothermal ablation is a new method in cardiac electrophysiology for the percutaneous catheter ablation of cardiac arrhythmias. Cryothermal mapping make possible the functional assessment of a particular site before permanent ablation. In this way the targeted tissue may be confirmed as safe for ablation. This is useful in high-risk ablation, for example next to the AV node. In this method pressurized liquid nitrogen is delivered to the tip of the ablation catheter. Cooling of the tip is temperature-controlled. Cryothermal balloons are also available, in addition to standard cryothermal catheters, for the isolation of pulmonary veins. The tissue freezing provides high catheter stability. Cryothermal lesions have a similar depth to radiofrequency energy, but area and volume of the lesions are reduced. Furthermore, they are well demarkated and the incidence of thrombus-formation is reduced. Cryothermal ablation has been evaluated for the treatment of AV-nodal reentry tachycardia (AVNRT), accessory pathways, atrial flutter, atrial fibrillation and ventricular tachycardias originating in the right ventricular outflow tract. Current experience indicates that the method is painless for the patient and safe. However, its use seems to be limited by a longer ablation time and lower efficacy. Further studies evaluating long-term success of cryothermal ablation are warranted. For high-risk ablations cryothermal energy is helpful and should be used for para-Hisian accessory pathways and difficult cases of AVNRT. It has a widely demonstrated safety profile. The clinical efficacy will have to be evaluated in further studies.

[Cardiac contractility modulation: a new option for treating systolic heart failure]. / Kardiale Kontraktilitätsmodulation: Eine neue Therapieoption bei systolischer Herzinsuffizienz.

Cardiac contractility modulation (CCM) is a recently developed electrical treatment for enhancing ventricular contractility by non-excitatory impulses applied during the absolute refractory period in advanced systolic heart failure, regardless of the presence of dyssynchrony and QRS prolongation. Implantation of a CCM device is comparable to pacemaker implantation. Three electrodes are placed in the heart via the subclavian vein. One electrode in the right atrium is used for sensing, while ventricular stimulation is done by two electrodes in the right ventricle. The FIX-CHF-4 trial was a randomized, double-blind and cross-over study in 164 patients with systolic heart failure and an ejection fraction 35%, in order to evaluate the effect of CCM treatment on exercise capacity and quality of life. After three months the patients' six-minute walk distance increased, while ejection fraction remained unchanged. Moreover, quality of life improved. CCM stimulation was found to be a safe method. In patients with heart failure and left ventricular systolic dysfunction exercise tolerance and quality of life may be improved by CCM. Further studies to determine morbidity and mortality during long-term CCM stimulation are indicated.

[Risks of non-prescription medication. Clobutinol cough syrup as a recent example]. / Risiken nicht verschreibungspflichtiger Medikamente. Aktuelles Beispiel Silomat Hustensaft.

INTRODUCTION: The arbitrary use of additional drugs other than prescribed medication is known to be a huge part of drug sales. However, the interactions of such non-prescription medication with any daily medication or concomitant diseases remain often unclear. Recently, in accordance with the decision of the competent authority in Germany, clobutinol (e.g. Silomat), a drug against non-productive cough was withdrawn in all countries worldwide in which this medication had been available. The drug had first been approved in 1961 and estimated to have had 200 million patient exposures. A recent clinical study revealed that clobutinol can prolong the QT interval compared to placebo and may thus cause cardiac tachyarrhythmias. Even in therapeutic doses (240 mg daily) this effect was seen in healthy volunteers. Furthermore, this study was prematurely discontinued because of an epileptic grand mal seizure in one volunteer, suggesting neurological side effects of clobutinol. DISCUSSION: Clobutinol prolongs the QT interval and may cause life-threatening arrhythmias. This should serve as a warning to doctors to be careful when prescribing non-prescription medication. CONCLUSION: Non-prescription drugs can be a potential risk for patients who are also taking other pharmaceutical preparations or having concomitant disease. This is because such drugs may cause harmful interactions, most of them previously unknown. All doctors should avoid unsupervised use of non-prescription medication.

[Natriuretic peptides--when should they be used in heart failure?]. / Natriuretische Peptide--wann ist die Bestimmung bei chronischer Herzinsuffizienz wirklich indiziert?

BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are widely being used as biomarkers in acute and chronic heart failure. These cardiac neurohormones are mainly being secreted from the left and right ventricles as a response to ventricular volume expansion, pressure overload and resultant increased wall tension. PROBLEM: Current application of natriuretic peptides is manifold. BNP and NT-proBNP are being used as screening parameters, diagnostic markers, and prognostic indicators or to monitor therapy. However, their usage to diagnose heart failure and possibly in future adjust therapy should not be uncritical. DISCUSSION: In the interpretation of natriuretic peptides it has to be considered that several factors such as age, sex, constitution and non-cardiac diseases like renal failure influence plasma levels. Natriuretic peptides may support diagnostics of heart failure in patients with unexplained dyspnea. However, biomarkers should not be used to replace conventional clinical evaluation. The use of natriuretic peptides for screening asymptomatic populations is inappropriate. A BNP-guided titration of heart failure medication is not yet warranted. BNP testing may be used only in selected situations for risk stratification since the prognostic value is still limited by a lack of clear usefulness in guiding clinical management. CONCLUSION: The measurement of natriuretic peptides is at present largely an addition in the diagnosis of acute heart failure, as long as possible errors in interpretation are taken into account.

[Therapy with glitazones--a risk for cardiovascular disease?]. / Therapie mit Glitazonen--ein kardiovaskuläres Risiko?

INTRODUCTION: Thiazolidinediones significantly reduce fasting plasma glucose and HbA (1c). These effects are due to improved insulin sensitivity by activating the nuclear PPAR-gamma (peroxisomal proliferator-activated receptors-gamma) and affection of different intracellular functions. The objective of this review was to analyse recently published studies and meta-analyses about thiazolidinediones, which suggested a significant cardiovascular risk associated with rosiglitazone therapy. Therefore clinicians have been left uncertain as to whether rosiglitazone should still be considered for the treatment of type-2-diabetes. DISCUSSION: An important side-effect of thiazolidinediones is fluid retention and edema. Therefore, heart failure NYHA I-IV is a contraindication for treatment with Thiazolidinediones. Pioglitazone shows favourable changes in lipid parameters like decrease of serum-triglycerides and increase of HDL-cholesterol, while Rosiglitazone temporarily increases LDL-cholesterol. In patients with type-2-diabetes mellitus and a high cardiovascular risk the PROactive study did not show a significant effect on the primary endpoint but significantly reduced the predefined secondary combined endpoint of total mortality, nonfatal myocardial infarction and stroke. Conversely, recently published meta-analyses suggested an increased cardiovascular risk and myocardial infarction rate associated with rosiglitazone therapy. CONCLUSION: Treatment with Rosiglitazone should be reconsidered because of a potential cardiovascular risk. In high risk patients without heart failure pioglitazone may be favoured for treatment of type 2 diabetes mellitus.

[Polypharmacy, compliance and non-prescription medication in patients with cardiovascular disease in Germany]. / Multimedikation, Compliance und Zusatzmedikation bei Patienten mit kardiovaskulären Erkrankungen.

BACKGROUND AND OBJECTIVE: The expenses of health insurances are continuously raising. With implementation of evidence-based medicine resulting in polypharmacy, compliance is decreasing and patients as well as physicians are facing unintentional drug interactions. Furthermore the arbitrary use of additional drugs apart from prescribed medication has to be considered. The objective of this study was to analyse polypharmacy, compliance and utilisation patterns for non-prescription medications (OTC) in patients with cardiovascular diseases. METHODS: 100 patients with cardiovascular diseases (45 women, 55 men, 58 - 87 years) were interviewed using a questionnaire. The compliance was determined by the Morisky-Score. RESULTS: 78 % of the patients received more than four pills every day (median 8.34). Most common products were beta-blockers (89 %), ACE-Inhibitors/Sartans (69 %) and aspirin (65 %). Only 52 % of the patients knew the indications of their medication. Although 83 % of the patients claimed to be absolutely compliant concerning their medication, the Morisky-Score revealed a high compliance only in 52 %. The compliance decreased significantly if the number of prescribed medication increased to more than four pills a day. 48 % of the patients took regularly non-prescription products, 35 % more than three additional products daily. Most commonly multivitamins, minerals, herbals and non-steroidal anti-inflammatory drugs were used. This non-prescription medication did not affect the compliance of the patients. CONCLUSIONS: Polypharmacy with more than four pills daily leads to a lower compliance and can therefore influence the implementation of guideline-medicine. Non-prescription medication is widely used and should be considered because of their potential side-effects and drug interactions.