Atrial fibrillation in congestive heart failure

Atrial fibrillation (AF) and heart failure (HF) are common and interrelated conditions, each promoting the other, and both associated with increased mortality. HF leads to structural and electrical atrial remodeling, thus creating the basis for the development and perpetuation of AF; and AF may lead to hemodynamic deterioration and the development of tachycardia-mediated cardiomyopathy. Stroke prevention by antithrombotic therapy is crucial in patients with AF and HF. Of the 2 principal therapeutic strategies to treat AF, rate control and rhythm control, neither has been shown to be superior to the other in terms of survival, despite better survival in patients with sinus rhythm compared with those in AF. Antiarrhythmic drug toxicity and poor efficacy are concerns. Catheter ablation of AF can establish sinus rhythm without the risks of antiarrhythmic drug therapy, but has important procedural risks, and data from randomized trials showing a survival benefit of this treatment strategy are still lacking. In intractable cases, ablation of the atrioventricular junction and placement of a permanent pacemaker is a treatment alternative; and biventricular pacing may prevent or reduce the negative consequences of chronic right ventricular pacing.

Individual dosage of digoxin in patients with heart failure

After the publication of DIG trial, the therapeutic target of serum digoxin concentration (SDC) for the treatment of heart failure (HF) has been lowered (0.40-1.00 ng/ml). However, the majority of equations to calculate digoxin dosages were developed for higher SDCs. Recently, a new equation was validated in Asian population for low SDCs by Konishi et al., but results in Caucasians are unknown.

Adherence to the medical regime in patients with heart failure

To assess adherence to medical treatment in patients with heart failure (HF) using a specific questionnaire and measurement of the serum concentration of digoxin.

Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study

Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy.

Efficacy, tolerability and risk factors for virological failure of darunavir-based therapy for treatment-experienced HIV-infected patients: the Swiss HIV Cohort Study

Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice.

Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir

Long-term side-effects and cost of HIV treatment motivate the development of simplified maintenance. Monotherapy with ritonavir-boosted lopinavir (LPV/r-MT) is the most widely studied strategy. However, efficacy of LPV/r-MT in compartments remains to be shown.

Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure

In the human body, over 1000 different G protein-coupled receptors (GPCRs) mediate a broad spectrum of extracellular signals at the plasma membrane, transmitting vital physiological features such as pain, sight, smell, inflammation, heart rate and contractility of muscle cells. Signaling through these receptors is primarily controlled and regulated by a group of kinases, the GPCR kinases (GRKs), of which only seven are known and thus, interference with these common downstream GPCR regulators suggests a powerful therapeutic strategy. Molecular modulation of the kinases that are ubiquitously expressed in the heart has proven GRK2, and also GRK5, to be promising targets for prevention and reversal of one of the most severe pathologies in man, chronic heart failure (HF). In this article we will focus on the structural aspects of these GRKs important for their physiological and pathological regulation as well as well known and novel therapeutic approaches that target these GRKs in order to overcome the development of cardiac injury and progression of HF.

S100A1 gene therapy for heart failure: a novel strategy on the verge of clinical trials

Representing the common endpoint of various cardiovascular disorders, heart failure (HF) shows a dramatically growing prevalence. As currently available therapeutic strategies are not capable of terminating the progress of the disease, HF is still associated with a poor clinical prognosis. Among the underlying molecular mechanisms, the loss of cardiomyocyte Ca(2+) cycling integrity plays a key role in the pathophysiological development and progression of the disease. The cardiomyocyte EF-hand Ca(2+) sensor protein S100A1 emerged as a regulator both of sarcoplasmic reticulum (SR), sarcomere and mitochondrial function implicating a significant role in cardiac physiology and dysfunction. In this review, we aim to recapitulate the translation of S100A1-based investigation from first clinical observations over basic research experiments back to a near-clinical setting on the verge of clinical trials today. We also address needs for further developments towards "second-generation" gene therapy and discuss the therapeutic potential of S100A1 gene therapy for HF as a promising novel strategy for future cardiologists. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy".

Complication and failure rates of fixed dental prostheses in patients treated for periodontal disease

Objectives: To evaluate the biological and technical complication rates of fixed dental prostheses (FDP) with end abutments or cantilever extensions on teeth (FDP-tt/cFDP-tt) on implants (FDP-ii/cFDP-ii) and tooth-implant-supported (FDP-ti/cFDP-ti) in patients treated for chronic periodontitis. Material and methods: From a cohort of 392 patients treated between 1978 and 2002 by graduate students, 199 were re-examined in 2005. Of these, 84 patients had received ceramo-metal FDPs (six groups). Results: At the re-evaluation, the mean age of the patients was 62 years (36.2–83.4). One hundred and seventy-five FDPs were seated (82 FDP-tt, 9 FDP-ii, 20 FDP-ti, 39 cFDP-tt, 15 cFDP-ii, 10 cFDP-ti). The mean observation time was 11.3 years; 21 FDPs were lost, and 46 technical and 50 biological complications occurred. Chances for the survival of the three groups of FDPs with end abutments were very high (risk for failure 2.8%, 0%, 5.6%). The probability to remain without complications and/or failure was 70.3%, 88.9% and 74.7% in FDPs with end abutments, but 49.8–25% only in FDPs with extensions at 10 years. Conclusions: In patients treated for chronic periodontitis and provided with ceramo-metal FDPs, high survival rates, especially for FDPs with end abutments, can be expected. The incidence rates of any negative events were increased drastically in the three groups with extension cFDPs (tt, ii, ti). Strategic decisions in the choice of a particular FDP design and the choice of teeth/implants as abutments appear to influence the risks for complications to be expected with fixed reconstruction. If possible, extensions on tooth abutments should be avoided or used only after a cautious clinical evaluation of all options.