Role of New Therapies in Reducing Mortality and Major Morbidity in Patients with Systolic Heart Failure

Though heart failure therapies, particularly for systolic heart failure, have developed rapidly and markedly during the past four decades, a need for additional relief persists and is progressively being met. Two new drugs have been approved for marketing in the United States within the past two years, and two other glucose lowering therapies for diabetes appear to have efficacy for heart failure as well. In addition, device therapy for heart failure has progressed markedly during the past 5 years, particularly in refinements of the indications and applications of devices to minimize symptoms and hospitalizations and to maximize survival. This chapter will outline these recent developments

Top ten risk factors for morbidity and mortality in patients with chronic systolic heart failure and elevated heart rate: the SHIFT risk model

Aims We identified easily obtained baseline characteristics associated with outcomes in patients with chronic heart failure (HF) and elevated heart rate (HR) receiving contemporary guideline-recommended therapy in the SHIFT trial, and used them to develop a prognostic model. Methods We selected the 10 best predictors for each of four outcomes (cardiovascular death or HF hospitalisation; all-cause mortality; cardiovascular mortality; and HF hospitalisation). All variables with p &#60; 0.05 for association were entered into a forward stepwise Cox regression model. Our initial analysis excluded baseline therapies, though randomisation to ivabradine or placebo was forced into the model for the composite endpoint and HF hospitalisation. Results Increased resting HR, low ejection fraction, raised creatinine, New York Heart Association class III/IV, longer duration of HF, history of left bundle branch block, low systolic blood pressure and, for three models, age were strong predictors of all outcomes. Additional predictors were low body mass index, male gender, ischaemic HF, low total cholesterol, no history of hyperlipidaemia or dyslipidaemia and presence of atrial fibrillation/flutter. The c-statistics for the four outcomes ranged from 67.6% to 69.5%. There was no evidence for lack of fit of the models with the exception of all-cause mortality (p = 0.017). Similar results were found including baseline therapies. Conclusion The SHIFT Risk Model includes simple, readily obtainable clinical characteristics to produce important prognostic information in patients with chronic HF, systolic dysfunction, and elevated HR. This may help better calibrate management to individual patient risk.</p

Crystal to Liquid-Crystal Transition Studied by Raman Scattering

Phase transitions of the nematic liquid crystal p-methoxy-benzylidine, p−n butyl-aniline were studied by recording the low-frequency Raman spectrum. The intensity of the lattice Raman bands undergoes abrupt change at the crystalline-to-nematic phase transition temperature, with an indication of a hysteresis. The band totally disappears at the isotropic (liquid) phase

Efficacy profile of ivabradine in patients with heart failure plus angina pectoris

Objectives: In the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT), slowing of the heart rate with ivabradine reduced cardiovascular death or heart failure hospitalizations among patients with systolic chronic heart failure (CHF). Subsequently, in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) slowing of the heart rate in patients without CHF provided no benefit for cardiovascular death or nonfatal myocardial infarction (primary composite end point), with secondary analyses suggesting possible harm in the angina subgroup. Therefore, we examined the impact of ivabradine in the patients with CHF plus angina in SHIFT. Methods: SHIFT enrolled adults with stable, symptomatic CHF, a left ventricular ejection fraction ≤35% and a sinus rhythm with a resting heart rate ≥70 bpm. Outcomes were the SHIFT and SIGNIFY primary composite end points and their components. Results: Of 6,505 patients in SHIFT, 2,220 (34%) reported angina at randomization. Ivabradine numerically, but not significantly, reduced the SIGNIFY primary composite end point by 8, 11 and 11% in the SHIFT angina subgroup, nonangina subgroup and overall population, respectively. Ivabradine also reduced the SHIFT primary composite end point in all 3 subgroups. Conclusions: In SHIFT, ivabradine showed consistent reduction of cardiovascular outcomes in patients with CHF; similar results were seen in the subgroup of SHIFT patients with angina

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

747-6 Myocardial Blood Flow in Aortic Regurgitation: Comparison of Global and Regional Blood Flow to Regional Wall Stresses

The impact of regional wall stress (WS) abnormalities on regional coronary flow (CBF) in aortic regurgitation (AR) is not known. However, the existence of such a relation is of potential importance since it might account in part for LV dysfunction and myocardial fibrosis seen in AR, and could suggest therapeutic strategies. We have previously developed and validated a method for calculating regional WS in the radial, circumferential and meridional directions from mid wall (MW) to apex (AP) and endocardium (ENDO) to epicardium (EPI) using a 4000 element model of the LV To define the relation of regional WS and CSF in AR, we applied our LV model in 5 normal (NL) and 4 AR rabbits in which regional CBF was measured using fluorescent microspheres. CBF and radial WS were as follows:CBF (ml/min/gm)Radial WS (×103dynes/cm2)MWAPMWAPNLEPI2.491.308329*ENDO2.090.74133133*AREPI1.821.82*8638*ENDO1.410.77*133133**=p&lt;0.001 (EPI vs ENDO for CSF, EPI to ENDO gradient in AR vs NL for radial WS)Thus, in AR, transmural CBF distribution varies significantly at the apex, while this tendency is less marked and less consistent in NL. No discernable transmural variation was apparent elsewhere in either group. These differences paralleled inversely the transmural variations in radial WS in AR vs NL. In contrast, meridional WS and circumferential WS were uniformly and significantly higher in AR than NL at apex and base (all p &lt; 0.001), a pattern which bore no relation to regional CSF pattern. Thus, regional radial WS influences regional transmural CBF pattern in AR. The importance of this relation to regional LV function and regional myocardial fibrosis in AR now must be assessed