acute heart failure is still associated with a high hospital mortality , which ranges between 4.0% and 12.7%.1 , 2 , 3 , 4 emergency physicians , cardiologists , intensivists , nurses , and other healthcare providers have to cooperate to provide optimal benefit . however , many treatment decisions are opinionbased , while relatively few are evidencebased .
according to the consensus paper on acute heart failure published in 2015 , the recommendation for intravenous vasodilator therapy is that it might be administered as an initial therapy for a symptomatic relief in cases when systolic blood pressure ( bp ) is normal to high ( 110  mmhg ) . alternatively
, sublingual nitrates may be considered.5 
  intravenous vasodilators are the second most commonly used agents in ahf patients .
their use was shown to be associated with a lower mortality , while a delay in administration was associated with a higher mortality.6 randomized controlled trial ( rct ) evidence comparing the clinical outcomes of intravenous vasodilators ( especially nitrates ) in ahf patients is rather limited , and its methodological quality is relatively low .
however , there is a consensus that intravenous vasodilators should be indicated in ahf with rather normal to high bood presure7 and should not be indicated in patients with sbp < 110  mmhg.5 
  recent phases iii and iv clinical trials have provided promising results with respect to potential management of acute heart failure .
these include trials relaxahf ( serelaxin),8 atomicahf trial ( omecantiv mecarbil),9 pronto ( clevidipine),10 trueahf ( ularitide)11 and artshf ( finerenone).12 
  the aim of the analysis was to compare the mortality rates of realworld ahf patients from the czech ahead registry1 , 13 with the published mortality rates of patients from the relaxahf trial . for the purpose of analysis , we had to divide the realworld population of czech ahf patients into two groups : the relaxcomparable group ( i.e. population of ahf patients in the ahead registry meeting the relaxahf criteria8 ) and the relaxnoncomparable group ( the remaining population of ahf patients in the ahead registry , not meeting those criteria ) .
furthermore , we divided the relaxcomparable group according to a recently published risk scoring system ahead14 in order to demonstrate that this simple tool can identify highrisk ahf patients who might potentially benefit from new therapeutic approaches in the future .
the study protocol complied with the declaration of helsinki and was approved by the multicentre ethics committee of university hospital brno ( brno , czech republic ) . written informed consent was obtained from all subjects to participate in the study .
the acute heart failure database ( ahead ) network registry was described previously.1 , 13 in short , the registry includes consecutive patients from 10 centres with 24  h catheterization laboratory services and a centralized care for patients with acute coronary syndromes ( previously described as 
ahead main ) and five regional centres without a catheterization laboratory ; nevertheless , the capacity of catheterization laboratories is sufficient to cover the entire population of the czech republic ( over 10 million inhabitants ) .
the following inclusion criteria were in accordance with the european guidelines for ahf issued in 2005 : signs and symptoms of ahf , confirmed leftventricular dysfunction ( systolic or diastolic ) and/or positive response to therapy.15 at the time of analysis , the ahead registry included 7318 hospitalizations for ahf ; out of which , 6242 were first hospitalizations for ahf ( for a given patient during the evaluated period of the ahead registry ) ; the dataset of first hospitalizations for ahf with available key variables for the analysis of comparability with the relaxahf trial included n  =  5856 patients ( figure 
 1 ) .
relaxahf was an international , doubleblind , placebocontrolled trial , enrolling patients admitted to hospital for acute heart failure who were randomly assigned to standard care plus 48  h intravenous infusions of placebo or serelaxin .
all patients had dyspnoea , congestion on chest radiograph , increased brain natriuretic peptide ( bnp ) or nterminal prohormone of bnp , mildtomoderate renal insufficiency , and systolic bp greater than 125  mmhg .
the 6  month mortality was 7.3% in the serelaxin group and 11.3% in the placebo group ( p  =  0.02).8 
  according to the relaxahf criteria , the evaluated cohort of 5856 ahf patients from the ahead registry was divided into two groups : the relaxcomparable group and the relaxnoncomparable group .
exclusion criteria for the relaxcomparable group included acute coronary syndrome , specific aetiology of ahf ( arrhythmias , severe form of valvular heart disesase , e.g. mitral or aortal regurgitation or stenosis , with severe bradycardia without overdose of betablockers , cardiac tamponade , hypertrophic , or restrictive cardiomyopathy , volume overload in kidney failure patients , overdose with negatively inotropic / chronotropic medication , heart failure after cardiac surgery and those with aortal dissection ) , systolic bp    125  mmhg , egfr  <  25  ml / min/1.73  m2 , and egfr  >  75  ml / min/1.73m2 .
mortality data were obtained from a centralized database of the ministry of health of the czech republic : the 30day mortality was 13.7% , and the 1year mortality 32.3% . in order to identify the subgroup of higherrisk patients in the relaxcomparable group , who might potentially benefit from new therapeutic approaches in future
, we divided this group of patients according to ahead , a recently published scoring14 system .
this score is based on the presence of comorbidities that worsen the patient 's prognosis : the patient obtains one point for the presence of each comorbidity , and the value of ahead score can thus range between 0 and 5 .
these monitored comorbidities are as follows : a  atrial fibrillation , anaemia ( h  haemoglobin level lower than 130  g / l for men and 120  g / l for women ) , e  elderly ( age 70  years ) , a  abnormal renal parameters ( creatinine 130  mol / l ) and d  diabetes mellitus .
standard descriptive statistics were applied in the analysis : absolute and relative frequencies were used for categorical variables , median values supplemented with 5th95th percentile range ( or mean and standard deviation ) were used for continuous variables .
the statistical significance of differences between data from the ahead registry and published data from the relaxahf trial was computed using ttest for continuous variables and chisquare test for categorical variables .
the analysis was performed with the use of spss 22.0.0.1 ( ibm corporation , 2014 ) .
the evaluated cohort ( n  =  5856 ) of ahf patients was divided according to the relaxahf criteria into two groups : the relaxcomparable group and the relaxnoncomparable group .
the baseline characteristics of both groups of patients recorded in the ahead registry compared with the published characteristics of the placebo group of patients from the relaxahf trial are shown in table 
 1 .
baseline characteristics of two ahead groups ( relaxcomparable and relaxnoncomparable ) compared to the relaxahf placebo group ace , angiotension converting enzyme ; arbs , angiotensin2 receptor blockers ; bp , blood pressure ; copd , chronic obstructive pulmonary disease ; pad , peripheral arterial disease . as compared with the relaxnoncomparable group ,
patients in the relaxcomparable group were older , had higher systolic , and diastolic blood pressure at admission and lower calculated creatinine clearance .
they had a higher number of comorbidities in their history , such as hypertension , stroke , or tia , peripheral artery disease , copd , and diabetes mellitus . at admission ,
they were more frequently treated by angiotensinconverting enzyme inhibitors , angiotensin2 receptor blockers , betablockers , and digoxin . as compared with the placebo group of patients from the relaxahf trial ( which was comparable with the seralaxintreated group8 ) ,
patients in the relaxcomparable group were older , had higher systolic , and diastolic blood pressure , and higher heart rate ; in terms of medical history , they had less frequently hypertension and atrial fibrillation but more frequently stroke or tia , smoking , and copd . at admission , patients from the relaxcomparable group were less frequently treated with betablockers and spironolactone . the kaplan
 meier survival estimation ( as shown in figure 
 2 ) demonstrates a significantly higher mortality of the relaxnoncomparable group as compared with the relaxcomparable group .
however , the 180day mortality of the relaxcomparable group is significantly higher in comparison with both relaxahf groups ( patients treated with seralaxin and placebo ) .
mortality of two groups of patients from acute heart failure database ( ahead ) registry ( relaxcomparable and relaxnoncomparable ) compared to mortality in the relaxahf study . according to the systolic blood pressure at admission ,
patients from both groups of the ahead registry were divided into six groups . in the relaxnoncomparable group ,
mortality in the relaxnoncomparable group was consistently higher across all systolic blood pressure categories in comparison with the relaxcomparable group ( figure 
 3 ) .
systolic blood pressure as a risk predictor for hospital mortality in acute heart failure database ( ahead ) registry .
overall , 33.8% of patients in the relaxcomparable group were treated with intravenous vasodilators ( vd ) , namely nitrates .
the hospital mortality of patients without vd therapy and with vd therapy was 3.1% and 2.9% , respectively , the 1month mortality was 7.1% and 6.1% , respectively , and the 1year mortality was 23.9% and 26.1% , respectively ( neither of these differences is statistically significant ) . according to the recently published risk scoring system ahead , patients from the relaxcomparable group were divided into three groups : lowrisk ( ahead score 01 ) , intermediaterisk ( score 23 ) , and highrisk ( score 45 ) .
figure 
 4 demonstrates that this simple stratification tool clearly differentiates lowrisk patients ( ahead score 01 ) from patients with a higher risk of death ( ahead score 23 and 45 ) , even within the first year after the patient 's discharge from hospital .
baseline characteristics of relaxcomparable group stratified by ahead score ace , angiotension converting enzyme ; arbs , angiotensin2 receptor blockers ; bp , blood pressure ; copd , chronic obstructive pulmonary disease ; pad , peripheral arterial disease .
mortality of patients in relaxcomparable group stratified by acute heart failure database ( ahead ) score .
our results highlight several very important points : ( i ) only 23% of all consecutive patients hospitalized with ahf met criteria of the large relaxahf trial ; ( ii ) mortality of patients who met criteria of the relaxahf trial ( relaxcomparable group ) is significantly lower in comparison to the rest of patients recorded in the ahead registry ( relaxahfnoncomparable group ) ; ( iii ) mortality of relaxcomparable group of patients from registry of consecutive ahf patients is significantly higher than mortality of patients in rct regardless to study treatment ; ( iv ) systolic bp at hospital admission significantly affects the prognosis of ahf patients .
based on our data , we were not able to confirm a reduction of mortality associated with the treatment by vasodilators , as it was previously demonstrated by results from the alarm registry , where the treatment by combination of diuretics and vasodilators led to a lower mortality in comparison to diuretics alone ( 7.6% and 14.2% , respectively , p  <  0.001).16 on the other hand , the ascend hf trial also did not confirm any statistically significant effect of nesiritidebased vasodilator therapy on ahfrelated mortality or rehospitalization.17 
  furthermore , our results demonstrated two to three times higher unadjusted mortality of patients with systolic bp    110  mmhg as compared with those with systolic bp  >  110  mmhg at admission .
similar results have been shown by the published data from the optimize hf registry , where a systolic bp lower than 100  mmhg was associated with three times higher hospital mortality rate in patients with normal ( 2.6% and 7.5% , respectively ) or with decreased renal functions ( 5.5% and 16.3% , respectively).18 
  finally , mortality analysis in the subgroup relaxcomparable showed that the ahead score is a simple tool that can easily identify higher risk patients who might potentially benefit from new therapeutic approaches in the future .
our results based on the czech registry ahead are fully consistent with the recently published results .
miro et al . demonstrated similar results from the spanish registry eahfe,19 and wang et al .
showed that approximately 2 out of 10 patients hospitalized because of ahf in the usa , latin america , or asiapacific are potentially eligible for the relaxahf criteria .
even after multivariate adjustement , relaxahf type of patients had lower mortality rates as compared with nonrelaxahf type of patients.20 
  two large rcts with vd therapy 
the relax ii trial is a multicentre , randomized , doubleblind , placebocontrolled phase iii study to evaluate the efficacy , safety , and tolerability of serelaxin when added to standard therapy in ahf patients .
the true ahf clinical trial has finished enrolment in spring 2015 , while the relax ii trial is supposed to finish enrolment in winter 2015/2016 .
results of both trials are expected to be available in 2016 , expectantly bringing the definitive answer on the role of vasodilators in acute heart failure treatment .
an increased value of the natriuretic peptide level was one of the important criteria for the enrolment in the relaxahf trial , as well as for the subsequent relax ii and true hf trials .
we could not use the natriuretic peptide levels because of a limited number of patients in which this parameter was known at the time of their admission .
however , we can assume that a low value of the natriuretic peptide would exclude lowrisk patients from the relaxcomparable group and that it could lead to an even higher mortality in the relaxcomparable group in comparison to relaxahf patients than we demonstrated in this study .
moreover , we were not able to exclude patients with acute infections that could lead to an acute decompensated heart failure .
according to results from the ahead registry , we can expect that about only 2025% of patients hospitalized because of ahf meet the criteria for a potential treatment with new vasodilator serelaxin .
significantly , lower mortality rates can be expected in participants of ongoing randomized clinical trials in comparison with realworld ahf patients .
ahead score is a simple tool that can easily identify higher risk patients who might potentially benefit from new therapeutic approaches in the future .
the new treatment of ahf patients with contraindication for vasodilator therapy remains the challenge for future research .
the work was supported by a project of conceptual development of research organization 65269705 ( university hospital brno ) funded by the ministry of health of the czech republic , by the grant muni / a/1362/2015 .
 abstractaimsthe randomized clinical trial relaxahf demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of ahf patients . 
 the aim of our study was to compare clinical characteristics and outcomes of patients from the ahead registry who met criteria of the relaxahf trial ( relaxcomparable group ) with the same characteristics and outcomes of patients from the ahead registry who did not meet those criteria ( relaxnoncomparable group ) , and finally with characteristics and outcomes of patients from the relaxahf trial.methods and resultsa total of 5856 patients from the ahead registry ( czech registry of ahf ) were divided into two groups according to relaxahf criteria : relaxcomparable ( n  =  1361 ) and relaxnoncomparable ( n  =  4495 ) . as compared with the relaxnoncomparable group , patients in the relaxcomparable group were older , had higher levels of systolic and diastolic blood pressure , lower creatinine clearance , and a higher number of comorbidities . 
 relaxcomparable patients also had significantly lower shortterm as well as longterm mortality rates in comparison to relaxnoncomparable patients , but a significantly higher mortality rate in comparison to the placebo group of patients from the relaxahf trial . using ahead score , 
 we have identified higherrisk patients from relaxcomparable group who might potentially benefit from new therapeutic approaches in the future.conclusionsonly about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin . 
 ahf patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial . 
Introduction
Methods
Results
Discussion
Conclusions
Conflict of interest
Funding