Angiotensin receptor blockers in heart failure after the ELITE II trial

Specific blockers of the angiotensin type1 receptor, angiotensin receptor blockers (ARBs), have been introduced as an alternative to angiotensin-converting enzyme inhibitors (ACEi) for the treatment of heart failure. In comparison with ACEi, ARBs are better tolerated and have similar effects on haemodynamics, neurohormones and exercise capacity. Early studies have suggested that ARBs might have a superior effect on mortality. However, the first outcome trial, ELITE II (Losartan Heart Failure Survival Study), did not show any significant difference between losartan and captopril in terms of mortality or morbidity. This commentary outlines the role of ARBs in the treatment of heart failure

Sudden death prevention in heart failure: The case of CIBIS III

CIBIS III completes a fundamental scientific phase of a sequence of large clinical trials (1-7) which has established the current therapeutic principles for the management of chronic heart failure (CHF) patients (8). These comprise the use of ACE inhibitors and beta- blockers. However, while ACE inhibitors, by antagonizing the synthesis of angiotensin II, found their natural pathway from hypertension into CHF, betablockers followed a controversial trail. They appeared effective in the BEHAT (9) trial after myocardial infarction (MI) even in patients with depressed left ventricular (LV) function. Nonetheless, the general view of CHF as an almost exclusively cardio-circulatory mechanical disease/remodelling led to the use of inotropic interventions, with non-infrequent negative consequences on mortality (10). Furthermore, this view prevented the conception of using antiadrenergic interventions in CHF which consequently remained a strong contraindication to the use of beta- blockers for many years. Beginning with CIBIS II, a number of trials have proven that beta-blocker therapy improves survival in CHF, with a specific action on arrhythmic sudden cardiac death (SCD) in patients with optimum background therapy, including the use of ACE inhibitors. This did not happen by chance, as a strong experimental ground had already existed.....

No effects on myocardial ischaemia in patients with stable ischaemic heart disease after treatment with ramipril for 6 months

OBJECTIVE: To assess the effects of a 6-month angiotensin-converting enzyme (ACE) inhibitor intervention on myocardial ischaemia. METHOD: We randomized 389 patients with stable coronary artery disease to double-blind treatment with ramipril 5 mg/day (n = 133), ramipril 1.25 mg/day (n = 133), or placebo (n = 123). Forty-eight-hour ambulatory electrocardiography was performed at baseline, and after 1 and 6 months. RESULTS: Relevant baseline variables were similar in all groups. Changes over 6 months in duration of ≥ 1 mm ST-segment depression (STD), total ischaemic burden and maximum STD did not differ significantly between the treatment groups. There was no difference in the frequency of adverse events between the groups. CONCLUSION: ACE inhibitor treatment has little impact on incidence and severity of myocardial ischaemia in patients with stable ischaemic heart disease

The association between glucometabolic disturbances, traditional cardiovascular risk factors and self-rated health by age and gender: A cross-sectional analysis within the Malmö Preventive Project

<p>Abstract</p> <p>Background</p> <p>The increased risk of cardiovascular disease (CVD) in diabetic compared to non-diabetic subjects seems to decrease with age. Whether this age-related reduction applies to CVD risk factors, and whether it is limited to established diabetes mellitus (DM) or also applies to pre-diabetic conditions are not well known.</p> <p>Methods</p> <p>Using a cross-sectional design we compared the strength of the correlation between glucometabolic disturbances (by grouping), CVD risk factor burden and self-rated health, in two age groups: middle-aged (57-69 years) and older (70-86 years) subjects, (63% men), participating in the Malmö Preventive Project Re-examination Study (n = 18,238). Simple (unadjusted) logistic regression analysis was applied to estimate between-group differences and trends. Interaction analysis was applied to estimate differences between age groups.</p> <p>Results</p> <p>CVD risk factor burden and the proportion of subjects reporting poor self-rated health increased with increasing glucometabolic disturbance for men and women in both age groups (p-trend < 0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for older women than for older men (p-interaction = 0.002). The slope of the trend curve for poor self-rated health was significantly steeper for middle-aged than for older men (p-interaction = 0.005), while no difference was observed between the age groups among women (p-interaction = 0.97).</p> <p>Conclusions</p> <p>We found no reduction in risk factor accumulation with increasing glucometabolic disturbance between middle-aged and older subjects. Our results indicate life-long CVD risk factor clustering with increased glucometabolic disturbance, and suggest that previously observed age-related reduction in excess CVD risk for subjects with DM might be due to a survival bias. However, our observations indicate more pronounced risk factor clustering and worse self-rated health with increased glucometabolic disturbance in older women than in older men.</p

Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care

Introduction: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). Methods: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). Results: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). Conclusions: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction

The effect of intravenous ferric carboxymaltose on health-related quality of life in patients with chronic heart failure and iron deficiency: a subanalysis of the FAIR-HF study

Aims Patients with chronic heart failure (CHF) show impaired health-related quality of life (HRQoL), an important target for therapeutic intervention. Impaired iron homeostasis may be one mechanism underlying the poor physical condition of CHF patients. This detailed subanalysis of the previously published FAIR-HF study evaluated baseline HRQoL in iron-deficient patients with CHF and the effect of intravenous ferric carboxymaltose (FCM) on HRQoL. Methods and results FAIR-HF randomized 459 patients with reduced left ventricular ejection fraction and iron deficiency, with or without anaemia, to FCM or placebo (2:1). Health-related quality of life was assessed at baseline and after 4, 12, and 24 weeks of therapy using the generic EQ-5D questionnaire and disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ). Baseline mean Visual Analogue Scale (VAS) score was 54.3 ± 16.4 and KCCQ overall summary score was 52.4 ± 18.8. Ferric carboxymaltose significantly improved VAS and KCCQ (mean differences from baseline in KCCQ overall, clinical and total symptom scores, P< 0.001 vs. placebo) at all time points. At Week 24, significant improvement vs. placebo was observed in four of the five EQ-5D dimensions: mobility (P= 0.004), self-care (P< 0.001), pain/discomfort (P= 0.006), anxiety/depression (P= 0.012), and usual activity (P= 0.035). Ferric carboxymaltose improved all KCCQ domain mean scores from Week 4 onward (P≤ 0.05), except for self-efficacy and social limitation. Effects were present in both anaemic and non-anaemic patients. Conclusions HRQoL is impaired in iron-deficient patients with CHF. Intravenous FCM significantly improved HRQoL after 4 weeks, and throughout the remaining study period. The positive effects of FCM were independent of anaemia statu

Rationale and design of Ferinject® Assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia

Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.v.) iron supplementation alone in patients with CHF and ID have shown improvements in symptom status. FAIR-HF (Clinical Trials.gov NCT00520780) was designed to determine the effect of i.v. iron repletion therapy using ferric carboxymaltose on self-reported patient global assessment (PGA) and New York Heart Association (NYHA) in patients with CHF and ID. This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF < 40% (NYHA II) or < 45% (NYHA III), ID [ferritin < 100 ng/mL or ferritin 100-300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5-13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject((R))) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class. This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia

Head to head comparisons of two modalities of perfusion adenosine stress echocardiography with simultaneous SPECT

<p>Abstract</p> <p>Background</p> <p>Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with ^99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia.</p> <p>Methods</p> <p>Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue^®infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest.</p> <p>Results</p> <p>In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR. SPECT showed evidence of ischemia in 13 out of 50 patients. There was no significant difference between AM and HR in detecting ischemia (p = 0.08). The agreement for AM and HR, compared to SPECT, was 93% and 96%, with Kappa values of 0.67 and 0.75, respectively (p < 0.001).</p> <p>Conclusion</p> <p>There was no significant difference between AM and HR in correctly detecting myocardial ischemia as judged by SPECT. This suggests that different types of RTP modalities give comparable data during RTP-ASE in patients with known or suspected CAD.</p

Quantitative detection of myocardial ischaemia by stress echocardiography; a comparison with SPECT

<p>Abstract</p> <p>Aims</p> <p>Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique angio-mode (AM), provides images for off-line perfusion quantification using Qontrast^®software, generating values of peak signal intensity (A), myocardial blood flow velocity (β) and myocardial blood flow (Axβ). By comparing rest and stress values, their respective reserve values (A-r, β-r, Axβ-r) are generated. We evaluated myocardial ischaemia by RTP-ASE Qontrast^®quantification, compared to visual perfusion evaluation with ^99mTc-tetrofosmin single-photon emission computed tomography (SPECT).</p> <p>Methods and Results</p> <p>Patients admitted to SPECT underwent RTP-ASE (SONOS 5500) using AM during Sonovue^®infusion, before and throughout adenosine stress, also used for SPECT. Visual myocardial perfusion and wall motion analysis, and Qontrast^®quantification, were blindly compared to one another and to SPECT, at different time points off-line.</p> <p>We analyzed 201 coronary territories (left anterior descendent [LAD], left circumflex [LCx] and right coronary [RCA] artery territories) in 67 patients. SPECT showed ischaemia in 18 patients and 19 territories. Receiver operator characteristics and kappa values showed significant agreement with SPECT only for β-r and Axβ-r in all segments: area under the curve 0.678 and 0.665; P < 0.001 and < 0.01, respectively. The closest agreements were seen in the LAD territory: kappa 0.442 for both β-r and Axβ-r; P < 0.01. Visual evaluation of ischaemia showed good agreement with SPECT: accuracy 93%; kappa 0.67; P < 0.001; without non-interpretable territories.</p> <p>Conclusion</p> <p>In this agreement study with SPECT, RTP-ASE Qontrast^®quantification of myocardial ischaemia was less accurate and less feasible than visual evaluation and needs further development to be clinically useful.</p

How to begin treatment in chronic heart failure? Results of CIBISIII

Aims To compare the effect of initial monotherapy with either bisoprolot or enalapril, followed by their combination, on mortality and hospitalization in patients with mild-to-moderate CHF. Methods and results One thousand and ten patients with mild-to-moderate CHF and left ventricular ejection fraction <= 35%, without ACE-inhibitor, beta-blocker, or angiotensin-receptor-blocker therapy were randomized to open-label monotherapy with either bisoprolot (target dose 10 mg od, n = 505) or enalapril (target dose 10 mg bid, n = 505) for 6 months, followed by their combination for 6-24 months. The combined primary endpoint was all-cause mortality or hospitalization; bisoprolol-first was considered non-inferior to enalapril-first if the upper limit of the 95% Cl for the absolute between-group difference was below +5%, corresponding to HR 1.17. In the intention-to-treat population, the primary endpoint occurred in 178 patients allocated bisoprotol-first vs. 186 allocated enalapril-first: absolute difference, -1.6%; 95% Cl, -7.6 to +4.4%; HR, 0.94; 95% Cl, 0.77-1.16. Thus, non-inferiority was demonstrated in the intention-to-treat population. In the per-protocol population, the primary endpoint occurred in 163 patients in the bisoprolol-first group vs. 165 in the enalapril-first group: absolute difference, -0.7%; 95% Cl, -6.6 to +5.1%; HR, 0.97; 95% Cl, 0.78-1.21. With bisoprolol-first, 65 patients died vs. 73 with enalapril-first (HR, 0.88; 95% Cl, 0.63-1.22; between-group difference P = 0.44), and 151 vs. 157 patients were hospitalized (HR, 0.95; 95% Cl, 0.76-1.19; between-group difference P = 0.66). Post hoc analysis of data from the first year indicated that a bisoprolol-first strategy reduced mortality by 31%, compared with an enalapril-first strategy (HR, 0.69; 95% CI, 0.46-1.02; between-group difference P = 0.065). Conclusion Initiating treatment with bisoprolot is as effective and well-tolerated as initiating treatment with enalapril. Post hoc analysis suggests that starting treatment with enalapril may reduce the risk of death, especially in the first year of treatment