Misconceptions and Facts About ‘Diastolic’ Heart Failure

Heart failure with preserved ejection fraction has become a fashionable diagnosis. An increasing number of elderly patients with dyspnea carry this diagnosis. Evaluation and management of these patients typically labeled as having “diastolic” heart failure are challenging, and misconceptions are common. No drug class has been shown to consistently provide outcome benefit. Therapeutic strategies based on the predominant pathophysiologic mechanism and stage of the disease currently remain the best option in tackling the perplexing syndrome of heart failure with preserved ejection fraction.     

In‐hospital worsening heart failure

Acute worsening heart failure (WHF) is seen in a sizable portion of patients hospitalized for heart failure, and is increasingly being recognized as an entity that is associated with an adverse in‐hospital course. WHF is generally defined as worsening heart failure symptoms and signs requiring an intensification of therapy, and is reported to be seen in anywhere from 5% to 42% of heart failure admissions. It is difficult to ascertain the exact epidemiology of WHF due to varying definitions used in the literature. Studies indicate that WHF cannot be precisely predicted on the basis of baseline variables assessed at the time of admission. Recent data suggest that some experimental therapies may reduce the risk of development of WHF among hospitalized heart failure patients, and this is associated with a reduction in risk of subsequent post‐discharge cardiovascular mortality. In this respect, WHF holds promise as a endpoint for acute heart failure clinical trials to better elucidate the benefit of targeted novel therapies. Better understanding of the pathophysiology and a consensus on the definition of WHF will further improve our epidemiological and clinical understanding of this entity.     

Cardiac Resynchronization—A Heart Failure Perspective

Over the past 15–20 years the development of new heart failure pharmacologic therapy has lowered mortality by 30–40% for this serious and prevalent clinical syndrome, within clinical trials conducted in patients with a dilated cardiomyopathy phenotype. However, over the past 5 years progress in the development of additional effective drugs has slowed, in part due to the success of neurohormonal inhibitors, on which background new therapies must be developed. That there is not an absolute ceiling on the development of new heart failure therapies has been convincingly recently demonstrated in electrophysiologic device trials, conducted on the background of maximal neurohormonal inhibition. Two trials, COMPANION and CARE‐HF, have demonstrated unambiguously that in advanced heart failure patients with a marker of mechanical intraventricular dyssynchrony, increased QRS duration, cardiac resynchronization therapy in the form of biventricular pacing can improve major clinical outcomes including mortality. In addition, COMPANION also demonstrated that the addition of an ICD further improved mortality reduction, by lowering the incidence of sudden death. These trials indicate that device/drug therapy is at least additive in the treatment of heart failure, and they herald a new era in the multi‐modality approach to therapeutics.     

Efficacy of short‐term dexamethasone therapy in acute‐on‐chronic pre‐liver failure

Aim: Acute‐on‐chronic pre‐liver failure (pre‐ACLF) is defined as a severe acute episode of chronic hepatitis B characterized by serum bilirubin of 171 µmol/L or more, alanine aminotransferase of five times or more the upper limit of normal and prothrombin activity of more than 40%, having a potential for progression to acute‐on‐chronic liver failure (ACLF). This study is to evaluate the efficacy of short‐term dexamethasone in pre‐ACLF. Methods: One hundred and seventy patients were assigned to dexamethasone therapy and control group at a ratio of 1:2. For the two groups, we compared biochemical indicators, the incidence of ACLF and mortality. The influential factors on the mortality of patients with pre‐ACLF were studied by Cox proportional hazards models. Results: The significantly lower incidence of ACLF and higher survival rate were observed in patients on dexamethasone therapy (8.9%, 96.4%, respectively) than in control patients (70.2%, 52.6%, respectively; P < 0.001). Dexamethasone treatment was an independent factor influencing the survival rate (P < 0.001, odds ratio = 0.055, 95% confidence interval = 0.013–0.225). During 4 weeks of treatment, serum bilirubin levels of survival patients were significantly lower in the dexamethasone group than control group. Conclusion: Five‐day dexamethasone therapy is effective in improving the liver function and survival rate of patients with pre‐ACLF.     

Place de l’échographie pelvienne réalisée par voie sus-pubienne dans l’exploration de l’insuffisance ovarienne prématurée

Objectives

The aim of the present study was to characterize women with premature ovarian failure (POF) by their ovarian ultrasonographic appearances using transabdominal technique to establish the relationship to clinical, hormonal status, and genetic analysis.

Patients and methods

We studied a cohort of 80 patients suffering from POF. The surface of the ovary was calculated and we identified the detection or not of follicles.

Results

The detection of the two ovaries by ultrasound was positive in 33 patients; only one ovary was identified in seven patients; none was noted in 40 patients. The surface of the ovaries ranged between 0.74 et 5.92 cm² (2.2 ± 1.13 cm²). Ultrasonography identified follicles in 23 patients (28.75%). The presence of follicles suggested at ultrasonography was detected in 14 cases (70%) in normal-sized ovaries (≥ 2 cm²) and in nine cases (45%) in small-sized ovaries (p = 0.1). No significative statistical difference was found between the ultrasonographic appearances and the type of amenorrhea, pubertal development, hormonal status (estradiol, testosterone and delta-4-androstendione) and the chromosomal analysis.

Conclusion

The clinical and hormonal status and the genetic analysis can’t predict the presence or not of follicles in the ovaries of patients with POF.     

Clinical trials update from the American College of Cardiology 2009: ADMIRE‐HF,PRIMA, STICH,REVERSE, IRIS,partial ventricular support,FIX‐HF‐5, vagal stimulation,REVIVAL‐3, pre‐RELAX‐AHF,ACTIVE‐A,HF‐ACTION,JUPITER, AURORA,and OMEGA

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the American College of Cardiology meeting in 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. ¹²³I‐mIBG myocardial scintigraphy was a good predictor of mortality in patients with heart failure in ADMIRE‐HF. In PRIMA, use of individualized target NT‐proBNP levels failed to improve outcomes compared with usual care in patients hospitalized with symptomatic heart failure. In the STICH trial, additional ventricular reconstruction surgery failed to improve outcomes in patients with ischaemic heart failure undergoing CABG. Cardiac resynchronization therapy may modify disease progression in patients with mild heart failure, according to data from REVERSE. Implantation of a defibrillator early after MI in high‐risk patients in the IRIS study failed to improve outcomes compared with usual care. Cardiac contractility modulation showed some beneficial effects on symptoms and exercise capacity in the unblinded FIX‐HF‐5 study. Data from pre‐RELAX‐AHF show that relaxin may have potential as a treatment for acute heart failure. HF‐ACTION showed that patients who complied with an exercise training regime achieved a better outcome, although this may be confounded by the ability of patients with a good prognosis to exercise for longer.     

Clinical trials update from the European Society of Cardiology–Heart Failure meeting 2015: AUGMENT‐HF,TITRATION, STOP‐HF,HARMONIZE, LION HEART,MOOD‐HF,and renin–angiotensin inhibitors in patients with heart and renal failure

This article provides an overview on the key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) annual meeting held in Seville, Spain in May 2015. Trials reported include AUGMENT‐AF (myocardial injections of calcium‐alginate hydrogel), a propensity score‐matched study of renin–angiotensin system antagonists in patients with HF and severe renal dysfunction, HARMONIZE (sodium zirconium cyclosilicate used to bind potassium), TITRATION, comparing two regimes for introducing LCZ696, STOP‐HF, a trial of intramyocardial stromal cell‐derived factor‐1, MOOD‐HF (escitalopram for patients with heart failure and depression), and LION HEART, a trial of intermittent levosimendan therapy. Unpublished reports should be considered as preliminary, since analyses may change in the final publication.     

Clinical trials update from the Heart Failure Society of America Meeting 2009: FAST,IMPROVE‐HF,COACH galectin‐3 substudy,HF‐ACTION nuclear substudy,DAD‐HF,and MARVEL‐1

This article presents findings and a commentary on late‐breaking trials presented during the meeting of the Heart Failure Society of America in September 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The FAST trial showed somewhat better performance of intrathoracic impedance for prediction of deterioration in patients with heart failure (HF) when compared with daily weighing. The IMPROVE‐HF study reported the benefits of education on the management of patients with systolic HF. Galectin‐3 appeared a useful method for improving risk stratification of patients with chronic HF in a substudy of the COACH trial. A nuclear substudy of the HF‐ACTION trial failed to demonstrate that resting myocardial perfusion imaging, a measure of myocardial scar and viability, was clinically useful. A small randomized controlled trial (DAD‐HF) suggested that the use of low‐dose dopamine in patients with acutely decompensated HF was associated with less deterioration in renal function and less hypokalaemia. The MARVEL‐1 trial raises further concerns about the safety of myoblast transplantation in ischaemic HF.     

Clinical trials update from the American Heart Association meeting 2009: HEAAL,FAIR‐HF,J‐CHF,HeartMate II,PACE and a meta‐analysis of dose‐ranging studies of beta‐blockers in heart failure

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Orlando, Florida in 2009. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. Patients with heart failure randomized to high‐dose losartan treatment (150 mg) in the HEAAL study had a reduced risk of death or heart failure hospitalization compared with patients in the low‐dose (50 mg) group. In FAIR‐HF, patients with heart failure and concomitant iron deficiency but without severe anaemia who received iron supplementation therapy demonstrated an improvement in symptoms at 24 weeks compared with placebo. The J‐CHF study was too small and was stopped too early to provide definitive evidence about the optimal dose of carvedilol for Japanese patients with heart failure. Results from the HeartMate II study suggest that continuous‐flow left ventricular assist devices may offer benefits over pulsatile‐flow devices for long‐term support in patients with advanced heart failure. In the PACE study, atrial synchronized right ventricular pacing induced adverse effects on left ventricular function compared with atrial synchronized biventricular pacing in patients with standard pacing indications and a normal ejection fraction.     

Interação Letal entre Síndrome Hemofagocítica e Insuficiência Cardíaca Recentemente Desenvolvida

Background:Hemophagocytic syndrome (HPS) ia s devastating hyperinflammatory syndrome. Heart failure (HF) with preserved ejection fraction (HFpEF) status is closely correlated with increased inflammation, both systemic and intramyocardial.Objectives:This study sought to determine mortality predictors and reliable follow-up parameters in HPS that developed HFpEF during the clinical course.Method:Thirty-nine patients, diagnosed as HPS, according to HLH 2004 diagnostic criteria, with an HScore of ≥169 and proven bone marrow aspiration or biopsy, were recruited retrospectively. Both traditional, serum C-reactive protein, albumin and ferritin levels with lymphocyte, and platelet counts, as well as non-traditional risk factors, neutrophil-to-lymphocyte count (NLR), monocyte-to-lymphocyte count (MLR), mean platelet volume (MPV), and N-Terminal pro-brain natriuretic peptide (NTproBNP), were investigated retrospectively. The relationship between time-changed laboratory values both among themselves and with mortality. The overall significance level was set at 5%.Results:This study showed that temporal change of cardiothoracic ratio (CTR), serum NTproBNP, ferritin, CRP, and albumin levels were detected as mortality predictors (p<0.05, for all) in the univariate analysis. Lymphocyte and platelet counts with NLR and MPV values were also significant (p<0.05). The relationship between NT-proBNP and increased systemic inflammatory markers proved to be significant. In addition to traditional risk factors, serum ferritin levels, NLR, MLR, and MPV levels also proved to be significantly correlated with each other.Conclusion:Accompanied by reliable follow-up parameters, rapid diagnosis and aggressive anti-inflammatory treatment with tight volume control can be life-saving in HPS patients who suffer from HFpEF. Close monitoring of inflammation may predict the outcome of patients suffering from HFpEF.