August 2017 at a Glance: Tailored Treatment, Acute Heart Failure and Cardiac Resynchronization

Ferreira et al. review treatment with mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF).1 Randomized controlled trials have shown that these drugs are effective in most of the patients with HF and reduced ejection fraction (HFrEF), including those with mild to moderate renal dysfunction or with hypokalaemia or mild hyperkalaemia.1 New MRAs and/or drugs preventing hyperkalaemia may further increase the indication to MRAs.2-4 Different from HFrEF, better patient selection seems warranted in those showing HF with preserved ejection fraction (HFpEF). The trial conducted in these patients, the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT), showed marked geographical differences.5, 6 Spironolactone had favorable effects in patients in the prespecified randomization stratum with high NT-proBNP levels at baseline, and these patients with HFpEF and high BNP levels may be considered as potential targets for treatment with MRAs.1, 7 Further indications to MRAs may come from studies in patients with acute HF at high risk of events and, on the opposite side of the spectrum, from studies in asymptomatic patients with increased markers of fibrosis, cardiac damage, or inflammation.1 In-hospital worsening HF (WHF) occurs in a meaningful proportion of patients with acute HF (AHF) and is associated with poorer post-discharge outcomes.8 It was analysed mostly in randomized controlled trials with few data from unselected patient populations. AlFaleh et al. describe the clinical characteristics and outcomes of patients who developed WHF during their hospitalization for AHF among the 2609 patients enrolled in a prospective AHF registry in Saudi Arabia. Worsening HF developed in 33.8% of the study participants and was associated with an increased length of hospital stay and with higher in-hospital, 30-day and long-term mortality rates.9 Demissei et al. studied the value of multiple biomarkers, measured at multiple time intervals, for the prediction of 180-day mortality in 1161 patients enrolled in the RELAX-AHF trial.10 With the exception of galectin-3, serial biomarker evaluation showed incremental predictive value over baseline measurements alone. Repeated measurement as early as day 2 was adequate for NT-proBNP and cystatin-C whereas further measurements on days 14 and 60 provided better prognostic value for high sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor 15 (GDF-15), soluble ST2 (sST2), and high sensitivity C-reactive protein (hs-CRP). Compared with a pre-specified baseline model, yielding a c-index of 0.79 for the prediction of 180-day mortality,11 the greatest prognostic gain was achieved with the combination of NT-proBNP, hs-cTnT, GDF-15, and sST2, with an increase in the c-index to 0.87 (95% confidence interval 0.83–0.91).10 Diuretic response is a major determinant of outcomes in patients with HF.12, 13 The different determinants of diuretic resistance have been studied using the measurement of diuretic clearance and natriuretic response in 50 patients with AHF undergoing intravenous bumetanide administration.14 An impairment in drug delivery to the nephron, such as that caused by reduced glomerular filtration rate, was not a major determinant of diuretic response whereas renal tubular resistance, defined by the relation between bumetanide excretion and natriuresis, accounted for 71% of this variability and was the main cause of diuretic resistance.14 Major advances in our knowledge of the Takotsubo syndrome have occurred in the last years.15 Its diagnosis, however, remains challenging, mostly with respect to its differentiation from acute coronary syndromes. Ghadri et al. have developed a clinical score for the diagnosis of Takotsubo syndrome in a derivation cohort from the International Takotsubo Registry, compared with patients admitted for acute coronary syndrome.16 The best model was based on seven variables, each with a specific score: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve for the resulting score was 0.971 in the derivation cohort and 0.901 in an independent validation cohort. Using a cut-off value of 40 score points, sensitivity was 89% and specificity 91% for the diagnosis of Takotsubo versus acute coronary syndrome.16 The prognostic value of mechanical dyssynchrony was assessed in 424 patients who participated in the echocardiographic substudy of the TOPCAT trial.17 Mechanical dyssynchrony was mainly defined on the basis of the standard deviation of the time to peak longitudinal strain. Worse dyssynchrony was associated with wider QRS, prior myocardial infarction, larger left ventricular volume and mass, and worse systolic and diastolic left ventricular function. It was associated with a poorer outcome in unadjusted analysis but not after adjusting for clinical, electrocardiographic and laboratory variables.17 Linde et al. conducted an individual patient meta-analysis of 1591 patients enrolled in three double-blind, randomized trials, comparing cardiac resynchronization therapy (CRT) programmed on or off, with respect to the predictors of an improvement of a clinical composite score (CCS) at 6 months after CRT.18 This score classifies the patients as improved, worsened, or unchanged based on mortality, HF hospitalization, cross-over from assigned randomization, New York Heart Association functional class, and the patients' self-assessment of their state. Multivariable modelling identified QRS duration and left ventricular ejection fraction as the only independent predictors of CRT clinical response. The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in left ventricular ejection fraction for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms.18