Elevated heart rate is a significant marker for mortality and morbidity in cardiovascular disease including heart failure. Despite background treatment with a beta-blocker, many patients with heart failure and low ejection fraction maintain a heart rate above 70 b.p.m. Ivabradine reduces heart rate directly through inhibition of the If ionic current.
SHIFT is a randomized, double-blind study designed to compare ivabradine with placebo on outcomes in patients with symptomatic chronic heart failure (NYHA class II–IV), left-ventricular ejection fraction ≤35%, and a prior hospitalization for worsening heart failure within the previous 12 months. Randomized treatment is given on top of guidelines-based therapy for chronic heart failure, including a beta-blocker at optimized dose. Resting heart rate at baseline must be ≥70 b.p.m. The primary endpoint is the composite of the time to first event of cardiovascular death or hospitalization for worsening heart failure. Secondary endpoints include all-cause, cardiovascular and heart failure mortality, and hospitalization. The randomized treatment period lasts approximately 12–48 months. The study will include approximately 6500 patients and will continue until ≥1600 primary endpoints have occurred. The first patient was randomized in October 2006, and the study is expected to end in 2010.
The SHIFT study will assess if a heart rate reduction by direct sinus node inhibition can reduce cardiovascular outcomes in patients with chronic heart failure and left-ventricular systolic dysfunction.
Cardiac death remains the principal cause of mortality in β-thalassemia major (β-TM). Echocardiography may provide additional information, incremental to haematological profile, both for guiding chelation therapy and to assess prognosis.
Between 1993 and 1995, 36 patients with β-TM and normal cardiac function and 25 normal volunteers underwent evaluation using resting and dobutamine stress echocardiography (DSE). Dobutamine stress echocardiography was performed at baseline and repeated after 2 years. The primary endpoint was cardiac mortality. During a 12-year observation period, seven patients (19%) died from heart failure. All seven deaths occurred among the cohort of 12 patients with median ferritin concentrations ≥2800 ng/mg. In addition, a resting left ventricular ejection fraction (LVEF) <60% was also associated with increased late mortality. In multivariate analysis, increased serum ferritin levels and reduced LVEF but not DSE or other haematological variables were independent survival determinants.
Resting LVEF provides prognostic information that is additional to ferritin levels among patients with β-TM.
We describe the prevalence and prognostic significance of heart failure (HF) complicating acute coronary syndromes (ACS) in patients enrolled in the Gulf Registry of Acute Coronary Events (Gulf RACE).
Gulf RACE is a prospective, multi-national study of all patients hospitalized with ACS in 65 centres in six Arab countries. Data were analysed based on HF on presentation (Killip class II/III) or during hospital stay. The study endpoint was all-cause in-hospital mortality. Of 8000 patients with ACS, 2009 (25%) had HF on presentation or during the hospital stay. Patients with HF were older, more often with co-morbid conditions, and less often treated with evidence-based therapies. Heart failure was associated with higher in-hospital mortality (7.9 vs. 0.9%, P < 0.001), which persisted after adjusting for age, gender, and presentation and treatment characteristics [adjusted odds ratio 4.1 (1.8–9.4)]. There was a significant interaction between age and the prognostic effect of HF on in-hospitality mortality, such that younger patients had a significantly higher increase in mortality related to HF (P for interaction = 0.002).
Heart failure complicates a substantial proportion of ACS admissions in the Arab Middle East and is associated with higher in-hospital death. Younger patients with ACS have a higher relative increase in mortality related to HF.
To compare the effects of lipophilic simvastatin and hydrophilic rosuvastatin on plasma adiponectin and glycated haemoglobin A1c (HbA1c) levels in patients with non-ischaemic chronic heart failure (NICHF).
Seventy-one stable outpatients with NICHF, who were already receiving standard therapy for CHF, were randomized to simvastatin (n = 35) or rosuvastatin (n = 36). Plasma levels of brain natriuretic peptide (BNP), total adiponectin, high-sensitive C-reactive protein, HbA1c, and oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, were measured before and 4 months after treatment with simvastatin or rosuvastatin. There was no difference in the baseline characteristics including left ventricular ejection fraction (LVEF) and biochemical parameters between the two groups. In both groups, plasma BNP levels and LVEF did not change after 4 months. Plasma levels of adiponectin and oxLDL did not change and HbA1c level was slightly increased (6.0 ± 0.9 vs. 6.1 ± 0.9%, P = 0.053) in the simvastatin group. In contrast, plasma adiponectin level was significantly increased (12.3 ± 7.3 vs. 14.0 ± 8.2 µg/mL, P = 0.012) concomitant with a significant reduction in oxLDL and HbA1c (oxLDL: 8.8 ± 4.7 vs. 7.6 ± 4.7 U/mL, P = 0.0059; HbA1c: 6.0 ± 0.7 vs. 5.9 ± 0.7%, P = 0.002) in the rosuvastatin group.
These findings suggest that hydrophilic rosuvastatin but not lipophilic simvastatin increases adiponectin and decreases HbA1c levels in patients with NICHF.
To verify whether controlling for indicators of disease severity and confounders represents a solution to the obesity paradox in chronic heart failure (CHF).
From a cohort of 1790 patients, we formed 230 nested matched triplets by individually matching patients with body mass index (BMI) > 30 kg/m2 (Group 3), BMI 20–24.9 k/m2 (Group 1) and BMI 25–29.9 kg/m2 (Group 2), according to NT-proBNP, age, sex, and NYHA class (triplet = one matched patient from each group). Although in the pre-matching cohort, BMI group was a significant univariable prognostic indicator, it did not retain significance [heart rate (HR): 0.91, 95% CI: 0.78–1.05, 2: 1.67] when controlled for group propensities as covariates. Furthermore, in the matched cohort, 1-year mortality and 3-year mortality did not differ significantly. Here, BMI again failed to reach statistical significance for prognosis, either as a continuous or categorical variable, whether crude or adjusted. This result was confirmed in the patients not selected for matching. NT-proBNP, however, remained statistically significant (log(NT-proBNP): HR: 1.49, 95% CI: 1.13–1.97, 2: 7.82) after multivariable adjustment.
The obesity paradox does not appear to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP remains an independent prognostic indicator of adverse outcome irrespective of obesity status.
To compare prognosis in patients with chronic obstructive pulmonary disease (COPD) with or without concomitant heart failure.
Patients aged 65 years or over with a general practitioner (GP)'s diagnosis of COPD but without a prior diagnosis of heart failure underwent an extensive diagnostic work-up including echocardiography and pulmonary function tests in the period 2001–03. An expert panel then confirmed the presence or absence of COPD according to the GOLD criteria and (previously undiagnosed) heart failure according to the criteria of the ESC heart failure guidelines. This cohort of 405 patients was followed up for a mean duration of 4.2 (SD 1.4) years. The GP's electronic medical files relating to the participants, including any specialist letters, were scrutinized until April 2007 for information about drug use, exacerbations of COPD, pneumonia, hospitalizations, death, and cause of death. The mean age of patients at the start of the study was 73.0 (SD 5.3) years, and 54% were male. The presence of newly detected heart failure significantly increased all-cause mortality independent of gender, age, history of ischaemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, smoking, and cardiovascular drug use at baseline (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2–3.6; P = 0.01).
Heart failure is a strong independent predictor of all-cause mortality in patients with a diagnosis of COPD.
Heart failure (HF) patients increasingly receive device therapy, either an implantable cardioverter defibrillator (ICD) or a biventricular pacemaker, also called cardiac resynchronization therapy (CRT), or a CRT device with an ICD (CRT-D). However, epidemiological data on the use of device therapy in Europe are limited.
Data on implantation rates for conventional pacemakers, ICD, CRT, and CRT-D in 15 Western European countries were obtained from the Eucomed Registry for the 5-year period 2004–2008. Implantation of conventional pacemakers increased by 9% in Europe over the 5 years (reaching 907/million in 2008) and there were significant differences between countries. Implantable cardioverter defibrillator implantations increased by 75% from 80/million in 2004 to 140/million in 2008, and differences between countries were larger than those for conventional pacemakers. Implantation rates for CRT-P alone increased slightly from 2004 to 2006, but remained at 25/million thereafter in Europe overall. The total number of CRT implants (CRT-P and -D) markedly increased from 46/million in 2004 to 99/million in 2008 (115%), but this was mainly due to more CRT-D implants, i.e. an increase in the proportion of CRT-D (from 55% in 2004 to 75% in 2008). Implantation rates for ICD, CRT, and CRT-D remained markedly different throughout the study period between countries.
Implantation rates of devices for HF, in particular ICD and CRT-D, have increased significantly between 2004 and 2008 in Europe, but there remain major differences between countries.
The ‘Hospital at home’ (HaH) model avoids hospital admission by transferring healthcare and treatment to the patient's home. We aimed to compare the effectiveness and direct healthcare costs of treating elderly patients with decompensated heart failure (HF) using HaH care vs. inpatient hospital care (IHC) in a cardiology unit.
Eighty patients aged over 65 years who presented at the emergency department with decompensated HF were randomly assigned to IHC or HaH. All patients were studied for 1 year. Seventy-one patients completed the study, of these 34 were admitted to cardiology and 37 received HaH care. No significant differences were found in baseline characteristics, including comorbidity, functional status, and health-related quality of life. Clinical outcomes were similar after initial admission and also after the 12 months of follow-up. Death or re-admission due to HF or another cardiovascular event occurred in 19 patients in IHC and 20 in HaH (P = 0.88). Changes in functional status and health-related quality of life over the follow-up period were not significantly different. The average cost of the initial admission was 4502 ± 2153 in IHC and 2541 ± 1334 in HaH (P < 0.001). During 12 months of follow-up, the average expenditure was 4619 ± 7679 and 3425 ± 4948 (P = 0.83) respectively.
Hospital at home care allows an important reduction in the costs during the index episode compared with hospital care, whilst maintaining similar outcomes with respect to cardiovascular mortality and morbidity and quality of life at 1 year follow-up.
Heart failure (HF) is a major public health issue and hypertension is a major predictor of HF. Observational studies have demonstrated a continuous and graded relationship between ‘normal’ systolic blood pressure (SBP) and cardiovascular disease. However, limited data are available on the relationship between normotensive SBP and the risk of HF.
To test the hypothesis that there is a graded relation between SBP and HF risk among subjects with normal SBP, we used data on 18 876 participants who were healthy and were free of HF at baseline. Incident HF cases were ascertained by annual follow-up questionnaires and validated through a review of medical records. Cox proportional hazard model was used to compute multivariable-adjusted hazard ratios with corresponding 95% confidence intervals. Between 1982 and 2008, 1098 cases of HF occurred. There was a 35% increased risk of HF among subjects with SBP 130–139 mmHg compared with people with optimal SBP (<120 mmHg). In addition, there was a linear trend in HF risk across the normal range of SBP.
Our findings suggest a linear relationship between normotensive SBP and HF risk. Strategies to prevent HF, such as lifestyle modification, should be emphasized across all blood pressure ranges.