Duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with ivabradine: findings from SHIFT

Aims: In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results: It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or ivabradine. Outcomes and the treatment effect of ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of ivabradine were independent of HF duration. Conclusions: Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials

The weak theory of monads

We construct a `weak' version EM^w(K) of Lack & Street's 2-category of monads in a 2-category K, by replacing their compatibility constraint of 1-cells with the units of monads by an additional condition on the 2-cells. A relation between monads in EM^w(K) and composite pre-monads in K is discussed. If K admits Eilenberg-Moore constructions for monads, we define two symmetrical notions of `weak liftings' for monads in K. If moreover idempotent 2-cells in K split, we describe both kinds of a weak lifting via an appropriate pseudo-functor EM^w(K) --> K. Weak entwining structures and partial entwining structures are shown to realize weak liftings of a comonad for a monad in these respective senses. Weak bialgebras are characterized as algebras and coalgebras, such that the corresponding monads weakly lift for the corresponding comonads and also the comonads weakly lift for the monads.Comment: 30 page

A Note on Queueing Systems Exposed to Disasters

We discuss queueing systems subject to total disasters. If the time intervals between successive disasters are i.i.d. random variables independent of arrival and service process and arrivals form a Poisson process, then the transient and the asymptotic analysis of such models may be based on Feller's Second Renewal Theorem. Several examples are given: the limiting behavior of M/G/1 in case of exponential disasters and its special cases M/M/1, M/M/1/K and M/M/infinity. (author´s abstract)Series: Research Report Series / Department of Statistics and Mathematic