Symptomatic Chronic Heart Failure Research Articles

Changing the treatment of heart failure with reduced ejection fraction: clinical use of sacubitril-valsartan combination.

Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.

Efficacy Profile of Ivabradine in Patients with Heart Failure plus Angina Pectoris

Objectives: In the Systolic Heart Failure Treatment with the I_f 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 I_f 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.

‘Cutting-edge’ medicines vs. affordable quality health care?

British Journal of Cardiac NursingVol. 11, No. 8 Guest Editorial‘Cutting-edge’ medicines vs. affordable quality health care?Nazish KhanNazish KhanSearch for more papers by this authorNazish KhanPublished Online:5 Aug 2016https://doi.org/10.12968/bjca.2016.11.8.370AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References British Heart Foundation (2016) Managing Heart Failure in the Community. http://tinyurl.com/gupbpkk (accessed 21 July 2016) Google ScholarHeart UK (2016) What is Familial Hypercholesterolaemia (FH)? http://tinyurl.com/gp7athb (accessed 21 July 2016) Google ScholarMcMurray JJ, Packer M, Desai AS et al.; PARADIGM-HF Investigators and Committees (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371(11): 993–1004. doi: https://doi.org/10.1056/NEJMoa1409077 Crossref, Google ScholarNHS Improvement (2011) A guide for review and improvement of hospital based heart failure services. http://tinyurl.com/h6yq45o (accessed 21 July 2016) Google ScholarNational Institute for Health and Care Excellence (2010) Chronic heart failure in adults: management. [CG108]. NICE, London. https://www.nice.org.uk/guidance/CG108 (accessed 21 July 2016) Google ScholarNational Institute for Health and Care Excellence (2016a) Sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction. [TA388]. NICE, London. https://www.nice.org.uk/Guidance/TA388 (accessed 21 July 2016) Google ScholarNational Institute for Health and Care Excellence (2016b) Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia. [TA393]. NICE, London. https://www.nice.org.uk/guidance/ta393 (accessed 21 July 2016) Google ScholarNational Institute for Health and Care Excellence (2016c) Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia. [TA394]. NICE, London. https://www.nice.org.uk/guidance/ta394 (accessed 21 July 2016) Google Scholar FiguresReferencesRelatedDetails 2 August 2016Volume 11Issue 8ISSN (online): 2052-2207 Metrics History Published online 5 August 2016 Published in print 2 August 2016 Information© MA Healthcare LimitedPDF download

▼ Sacubitril valsartan for heart failure

▼ Sacubitril valsartan (Entresto—Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.1 It is described as an angiotensin...

Effectiveness of Cardiac Rehabilitation for Prevention and Treatment of Sarcopenia in Patients with Cardiovascular Disease - A Retrospective Cross-Sectional Analysis.

Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. This study aimed to clarify the clinical characteristics of sarcopenia and to investigate the effects of comprehensive cardiac rehabilitation (CCR), including nutrition, physical exercise and medication, in patients with cardiovascular disease (CVD). We retrospectively studied 322 inpatients with CVD (age 72±12 years). Muscle mass, muscle strength and physical performance were assessed before and after exercise training in patients with and without sarcopenia, which was defined as either a gait speed of <0.8 m/s or reduced handgrip strength (<26 kg in males and <18 kg in females), together with lower skeletal muscle index (SMI) (<7.0 kg/m2 in males and <5.7 kg/m2 in females). The actual daily total calorie and nutrient intake was also calculated. Sarcopenia was identified in 28% of patients with CVD, these patients having a higher prevalence of symptomatic chronic heart failure and chronic kidney disease. SMI was significantly associated with protein intake and statin treatment. The ratio of peak VO2 and SMI was significantly higher in the statin treatment group. Handgrip strength, gait speed, leg weight bearing index, and nutritional intake improved after exercise training in patients both with and without sarcopenia. The present findings suggest that CCR is a promising strategy for prevention and treatment of sarcopenia in patients with CVD.

Sacubitril/valsartan for the treatment of heart failure

Sacubitril/valsartan (Entresto) is a new combined formulation licensed for the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction. This articles summarises its indications, efficacy and adverse effects.

Ivabradine in Management of Heart Failure: a Critical Appraisal.

Elevated resting heart rate has been linked to poor outcomes in patients with chronic systolic heart failure. Blockade of funny current channel with ivabradine reduces heart rate without inotropic effects. Ivabradine was recently approved by US Food and Drug Administration for patients with stable, symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%, who are in sinus rhythm with resting heart rate (HR) ≥ 70bpm and either are on maximally tolerated doses of beta-blockers, or have a contraindication to beta-blockers. This article will review and evaluate the data supporting the use of ivabradine in patients with HF and explore its mechanisms and physiologic effects.

Impact of Physical Inactivity on Mortality in Patients With Heart Failure

The impact of physical inactivity on heart failure (HF) mortality is unclear. We analyzed data from the HF Adherence and Retention Trial (HART) which enrolled 902 patients with New York Heart Association class II/III HF, with preserved or reduced ejection fraction, who were followed for 36 months. On the basis of mean self-reported weekly exercise duration, patients were classified into inactive (0 min/week) and active (≥1 min/week) groups and then propensity score matched according to 34 baseline covariates in 1:2 ratio. Sedentary activity was determined according to self-reported daily television screen time (<2, 2 to 4, >4 h/day). The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. There were 196 inactive patients, of whom 171 were propensity matched to 342 active patients. Physical inactivity was associated with greater risk of all-cause death (hazard ratio [HR] 2.01, confidence interval [CI] 1.47 to 3.00; p <0.001) and cardiac death (HR 2.01, CI 1.28 to 3.17; p = 0.002) but no significant difference in HF hospitalization (p = 0.548). Modest exercise (1 to 89 min/week) was associated with a significant reduction in the rate of death (p = 0.003) and cardiac death (p = 0.050). Independent of exercise duration and baseline covariates, television screen time (>4 vs <2 h/day) was associated with all-cause death (HR 1.65, CI 1.10 to 2.48; p = 0.016; incremental chi-square = 6.05; p = 0.049). In conclusion, in patients with symptomatic chronic HF, physical inactivity is associated with higher all-cause and cardiac mortality. Failure to exercise and television screen time are additive in their effects on mortality. Even modest exercise was associated with survival benefit.

Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study

Autonomic regulation therapy (ART) with chronic vagus nerve stimulation improves ventricular function in patients with chronic heart failure, but its effects on quantitative T-wave alternans (TWA), ventricular tachycardia (VT), baroreflex sensitivity, and autonomic tone remained unknown. Effects on TWA, a marker of risk of life-threatening arrhythmias; heart rate turbulence (HRT), an indicator of baroreflex sensitivity; heart rate variability; and VT incidence were studied in 25 patients with chronic symptomatic heart failure and reduced ejection fraction enrolled in the ANTHEM-HF study (NCT01823887). Twenty-four-hour ambulatory electrocardiographic recordings made before ART system (Cyberonics, Inc., Houston, TX) implantation involving the left or right vagus nerve and after 6 and 12 months of chronic therapy (10-Hz frequency, 250-μs pulse width, maximum tolerable current amplitude after 10 weeks of titration) at low-intensity (<2 mA; n = 10, 40%) or high-intensity (≥2 mA; n = 15, 60%) stimulation levels were analyzed. At 12 months, peak TWA levels were reduced by 29% from 71.0 ± 4.6 to 50.5 ± 1.8 μV (P < .0001). The number of patients with severely abnormal TWA (≥60 μV) was reduced by 76% from 17 to 4 (P < .0005), and the number of patients with nonsustained VT decreased by 73% from 11 to 3 (P < .025). HRT slope (P < .025), high frequency heart rate variability (HRV) (P = .05), and square root of the mean squared differences of successive normal-to-normal interval HRV (P = .013) increased. The mean heart rate derived from 24-hour Holter electrocardiograms decreased by 10% from 77 ± 2 to 69 ± 2 beats/min (P = .0002). HRT onset was unchanged. Chronic ART in patients with symptomatic heart failure improves cardiac electrical stability, as reflected by reduced TWA levels and heart rate, suppresses VT, and increases baroreceptor sensitivity. These observations deserve study in a larger population.

Abstract 16571: The Potential Impact of Expanding Cardiac Rehabilitation Coverage in Heart Failure: Insights From Get With the Guidelines Heart Failure

Background: In February 2014, coverage for cardiac rehabilitation (CR) was expanded by Centers for Medicare &amp; Medicaid to include patients with chronic symptomatic heart failure (HF) on optimal medical therapy with ejection fraction &lt;35%. Thus, we sought to characterize the patient population newly eligible for CR based on the expanded criteria and their associated outcomes. Methods: We analyzed the Get With The Guidelines-HF registry linked to Medicare claims data from 2008-2012 to assess three groups of patients age 65 or older: previously eligible (due to prior MI, CABG, stable angina, heart valve surgery, or PCI in the previous 12 months), newly eligible, and ineligible for CR. Ineligible patients met neither criteria. Incidence rate was calculated with Kaplan-Meier estimates and Cox proportional hazard models were used to determine the association of events. Results: Among 51,665 HF patients discharged alive, 27.2% (n=14,053) were newly eligible and 14.5% were previously eligible for CR (n=7477). Newly eligible patients were more likely to be black, have atrial fibrillation and EF &lt; 35%, while having fewer previous hospitalizations than patients previously eligible for CR. Newly eligible and ineligible patients had similar risk for 1-year mortality compared with those previously eligible (adjusted Hazard Ratio [HR] 0.95, 95% Confidence Interval [CI] 0.88-1.02, p-value=0.13 and [HR] 1.05, 95% [CI] 0.98-1.13, p-value=0.17, respectively). However, newly eligible and ineligible patients had lower risk for 1-year readmission compared with those previously eligible (adjusted [HR] 0.89, 95% [CI] 0.85-0.93, p-value&lt;0.001 and [HR] 0.94, 95% [CI] 0.90- 0.98, p-value&lt;0.001). Conclusions: The extension of coverage for cardiac rehabilitation has tripled the potentially eligible HF population. As these newly eligible patients are at high risk for adverse outcomes, cardiac rehabilitation should be considered.

Abstract 17891: Impact of Physical Activity and Sedentary Time on Heart Failure Outcomes

Introduction: The impact of physical inactivity and sedentary time on heart failure (HF) outcomes in patients not participating in exercise program is unclear. Hypothesis: Physical inactivity and sedentary time are associated with worse HF outcomes. Methods: We analyzed data from the multicenter, HF Adherence and Retention Trial (HART) which enrolled 902 NYHA - II/III HF patients with preserved or reduced ejection fraction, followed for 36 months. Based on the mean weekly purposeful physical activity duration, patients were classified into inactive (0 min/wk), partially active (1-90 min/wk), and active (&gt;90min/wk) groups. Patients were also classified according to average daily sedentary television (TV) time into &lt;2 hrs/d, 2-4 hrs/d, and &gt;4 hrs/d groups. Study groups were propensity score matched according to 33 baseline covariates in 1:1:1 ratio. The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. Results: There were 196 inactive, 341 partially active and 365 active patients, of whom 492 (164 in each group) were successfully propensity matched. Physical inactivity was associated with higher risk of death and cardiac death than any level of physical activity, Fig 1. There was no significant difference in HF hospitalization. Furthermore, 465 subjects were propensity matched into three sedentary TV time groups (155 in each group). Sedentary TV time &gt;4 hrs/d was independently and incrementally associated with all-cause death (Δ χ 2 = 6.05; P=0.049), beyond physical activity time, Fig 1. There was no significant difference in mortality between &lt;2 and 2-4 hrs/d sedentary TV time groups, after adjusting to physical activity time, Fig 2. Conclusions: In symptomatic chronic HF patients, physical inactivity is associated with higher all-cause and cardiac mortality. Modest purposeful physical activity was associated with survival benefit. Extended sedentary time was associated incremental increased mortality.

Shenfu decoction as adjuvant therapy for improving quality of life and hepatic dysfunction in patients with symptomatic chronic heart failure

Ethnopharmacological relevanceShenfu decoction (SFD) is a water extract of the dried root or root stalk of Panax ginseng C. A. Mey (Asian ginseng) and the lateral root of Aconitum carmichaeli Debx (prepared by Fuzi, Heishunpian in Chinese). It has been used to treat heart failure for over a thousand years. The main active components of SFD, ginsenosides and higenamine, enhance heart contractility, increase the coronary blood supply, improve ischemic myocardial metabolism, scavenge free radicals and protect myocardial ultrastructure. Aim of the studyTo investigate the effect of SFD on quality of life (QOL) and hepatic function in symptomatic chronic heart failure (CHF) patients. Materials and methodsForty patients enrolled in the study were randomized into two groups: an SFD group (18 cases) and a control group (22 cases). All the patients received standard heart failure therapy, and the SFD group patients were also treated with Shenfu granules for 14 days as an adjunctive therapy. The effects of SFD on QOL, plasma alanine aminotransferase (ALT) level, cardiac function, left ventricular ejection fraction (LVEF) and tumor necrosis factor-α (TNF-α) level were studied. ALT threshold in hepatic injury are 21U/L for men and 17U/L for women. ResultsMinnesota Living with Heart Failure Questionnaire (MLHFQ) scores were improved by 35.27±10.72 vs. 23.87±11.96 in the SFD and control groups respectively (p<0.01). Subgroup analysis of the MLHFQ results demonstrated that both physical and emotional scores were significantly higher in the SFD group (21.00±5.66 vs. 16.75±6.25, p<0.05; 4.64±4.84 vs. 1.13±2.85, p<0.05). Circulating ALT was significantly decreased by SFD (13.3IU/L vs. 0.6IU/L, p<0.01). The grading of cardiac function and LVEF were increased by 1.6±0.5 vs. 1.1±0.3 and 18%±13% vs. 8%±8% in the SFD and control groups respectively (p<0.05 and p<0.05). The level of TNF-α declined more in SFD than control group (64.8±5.0 to 57.6±4.1, p<0.05; vs. 61.6±5.9 vs. 57.7±3.2. p>0.05). ConclusionCompared with standard heart failure treatment, oral SFD as an adjuvant therapy significantly improved QOL and hepatic injury in CHF patients.

Circulating thrombospondine-2 in patients with moderate-to-severe chronic heart failure due to coronary artery disease.

Chronic heart failure (CHF) remains a leading cause of morbidity and mortality. In the current study, we aimed to evaluate the predictive value of circulating thrombospondin-2 (TSP-2) for cumulative survival in patients with ischemic CHF due to coronary artery disease (CAD). The results showed that during a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repeatedly. The median circulating levels of TSP-2 in patients who survived and those who died were 0.63 ng/mL (95%CI=0.55-0.64 ng/mL) and 1.03 ng/mL (95% CI=0.97-1.07 ng/mL) (P<0.001). Circulating TSP-2 independently predicted all-cause mortality (OR=1.27; 95%CI=1.08-1.59; P=0.002), CHF-related death (OR=1.16; 95%CI=1.02-1.50; P<0.001), and also CHF-related rehospitalization (OR=1.12; 95%CI=1.07-1.25; P<0.001). In conclusion, among CAD patients with symptomatic CHF, increased circulating TSP-2 is correlated with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization.

Circulating thrombospondin-2 in patients with moderate-to-severe chronic heart failure due to coronary artery disease

Chronic heart failure (CHF) remains a leading cause of morbidity and mortality. In the current study, we aimed to evaluate the predictive value of circulating thrombospondin-2 (TSP-2) for cumulative survival in patients with ischemic CHF due to coronary artery disease (CAD). The results showed that during a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repeatedly. The median circulating levels of TSP-2 in patients who survived and those who died were 0.63 ng/mL (95%CI = 0.55-0.64 ng/mL) and 1.03 ng/mL (95% CI = 0.97-1.07 ng/mL) (P<0.001). Circulating TSP-2 independently predicted all-cause mortality (OR = 1.27; 95%CI = 1.08–1.59; P = 0.002), CHF-related death (OR = 1.16; 95%CI = 1.02–1.50; P<0.001), and also CHF-related rehospitalization (OR = 1.12; 95%CI = 1.07–1.25; P<0.001). In conclusion, among CAD patients with symptomatic CHF, increased circulating TSP-2 is correlated with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization.

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.

Drug therapy for heart failure in older patients-what do they want?

Chronic heart failure (CHF) is predominantly seen in older patients, and therefore real life medicine often requires the extrapolation of findings from trials conducted in much younger populations. Prescribing patterns and potential benefits in the elderly are heavily influenced by polypharmacy and co-morbid pathologies. Increasing longevity may become less relevant in the frail elderly, whereas improving quality of life (QoL) often becomes priority; the onus being on improving wellbeing, maintaining independence for longer, and delaying institutionalisation. Specific studies evaluating elderly patients with CHF are lacking and little is known regarding the tolerability and side-effect profile of evidence based drug therapies in this population. There has been recent interest on the impact of heart rate in patients with symptomatic CHF. Ivabradine, with selective heart rate lowering capabilities, is of benefit in patients with CHF and left ventricular systolic dysfunction in sinus rhythm, resulting in reduction of heart failure hospitalisation and cardiovascular death. This manuscript will focus on CHF and the older patient and will discuss the impact of heart rate, drug therapies and tolerability. It will also highlight the unmet need for specific studies that focus on patient-centred study end points rather than mortality targets that characterise most therapeutic trials. An on-going study evaluating the impact of ivabradine on QoL that presents a unique opportunity to evaluate the tolerability and impact of an established therapy on a wide range of real life, older patients with CHF will be discussed.

Drug therapy for patients with systolic heart failure after the PARADIGM-HF trial: in need of a new paradigm of LCZ696 implementation in clinical practice.

Heart failure represents a primary cause of morbidity and mortality in older people and despite significant therapeutic advances, it is still characterized by important unmet needs, thus remaining a challenging field of clinical research. The recent PARADIGM-HF trial compared the novel compound LCZ696, a combination of the angiotensin receptor blocker valsartan and the neprilysin inhibitor sacubitril, versus the angiotensin-converting enzyme inhibitor enalapril in 8,442 patients with symptomatic chronic systolic heart failure. LCZ696 led to a 20% reduction in the rate of death or hospitalization for heart failure and a 16% reduction in the rate of all-cause death compared to enalapril at 3.5 years of follow-up. Despite those impressive results, the clinical application of this novel agent that requires the substitution of a cornerstone of current heart failure therapy, the angiotensin-converting enzyme inhibitors, should follow careful steps as imposed by the study design, the recruited population and the outcome in specific patient subgroups. Further insights into the effects of LCZ696 will be provided by the ongoing PARAGON-HF trial in patients with diastolic heart failure.

Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial.

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96–1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19–2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and β-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11–1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01–2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24–2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and β-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

Utility of Biomarkers in Contemporary Management of Chronic Heart Failure

The current interest in guided-based therapy of acutely decompensated and chronic heart failure (CHF) is steadily increased. The measurements of circulating levels of brain natriuretic peptide (BNP) and N-terminal pro-hormone of BNP (NT-pro-BNP) to be risk stratified of the patients with symptomatic CHF is not widely approached in routine clinical practice. Likewise several conceptual, methodological, and as a result practical limitations of the natriuretic peptideguided therapy are not able to fulfilled change the contemporary strategic approach based on symptoms and echo-guided treatment of CHF. Clinically significant biological variability of natriuretic peptide level, high cost and slow time-course, as well as the lack of conclusive scientific evidence within long-term period of intensive scientific investigations may not support idea about needing new biological markers or constructing novel combinations for multiple biomarker predictive score and biomarker guided-based therapy. The review is dedicated to consideration of potency and clinical advantages of novel strategic approach in the field of CHF treatment based on serial measurements of biomarkers and creating optimal its combinations.

Rationale and design of the CONFIRM-HF study: a double-blind, randomized, placebo-controlled study to assess the effects of intravenous ferric carboxymaltose on functional capacity in patients with chronic heart failure and iron deficiency.

Iron deficiency (ID) is a common co-morbidity associated with chronic heart failure (CHF), which has unfavourable clinical and prognostic consequences. In Ferinject Assessment in Patients with IRon Deficiency and Chronic Heart Failure (FAIR-HF), the treatment with i.v. ferric carboxymaltose (FCM) improved symptoms and quality of life over a 24 week period. Ferric CarboxymaltOse evaluatioN on perFormance in patients with IRon deficiency in coMbination with chronic Heart Failure (CONFIRM-HF) was designed to test a simplifieddosage scheme of FCM during a longer follow-up period. CONFIRM-HF, a double-blind, multi-centre, prospective, randomized, two-arm study, enrolled ambulatory patients with symptomatic CHF [New York Heart Association (NYHA) class II/III] with left ventricular ejection fraction ≤45%, BNP >100 pg/mL, or NT-proBNP >400 pg/mL, presence of ID [defined as ferritin <100 ng/mL, or ferritin 100-300 ng/mL if transferrin saturation (TSAT) <20%], and haemoglobin (Hb) <15 g/dL. Patients were randomized 1:1 to treatment with FCM or placebo for 52 weeks. Primary endpoint is change in 6-minute walk test (6MWT) distance from baseline to Week 24. Secondary endpoints are: change in 6MWT from baseline to Weeks 6, 12, 36, and 52; Patient Global Assessment score at Weeks 6, 12, 24, 36, and 52; and change from baseline to Weeks 6, 12, 24, 36, and 52 in NYHA class, fatigue score, and quality of life. Safety endpoints include overall safety over the treatment period of 52 weeks. Study medication was administered in single doses as undiluted bolus injection of up to 1000 mg of iron or normal saline at Day 0 and Week 6 up to iron repletion. Further doses of study medication could be administered at Weeks 12, 24, and 36 if a patient still had ID. Overall, 304 patients were recruited in 41 centres in nine countries. This study will provide further information on the efficacy and safety of iron therapy with i.v. FCM in CHF patients with ID over a 1 year period using a simplified dosing scheme.