the online version of this article ( doi:10.1007/s12471 - 015 - 0666 - 9 ) contains supplementary material , which is available to authorized users . adults with congenital heart disease ( chd ) have a lower life expectancy than their healthy counterparts , especially when pulmonary arterial hypertension ( pah ) develops [ 27 ] . pah - specific therapy has become the cornerstone in the management of these patients because of its beneficial effects on disease symptoms , haemodynamics and quality of life ( qol ) [ 3 , 810 ] . however , life expectancy and qol still remain markedly impaired . in patients with acquired heart failure , several studies found an association between baseline qol and mortality [ 11 , 12 ] . in addition , a decrease in qol over time was significantly associated with increased mortality in these patients , suggesting qol may identify patients in need for interventions to improve their survival . furthermore , several studies in acquired heart failure revealed that survival and qol can be improved by exercise training [ 1416 ] . thus , qol has the potential to serve as both an important determinant for mortality and a therapeutic target for treatment . the current study aims to investigate whether a decrease in qol in adult pah - chd patients is associated with late mortality . this was a prospective multicentre observational study of adult patients with pah associated with chd , including patients with down s syndrome [ 17 , 18 ] , referred for pah - specific therapy between january 2005 and may 2013 . the current qol study was part of an ongoing non - randomised trial on pah - specific therapy in pah - chd patients . patients with all kinds of structural heart defects , including closed defects , could be enrolled . pah was defined upon the echocardiographic pah probability ( tricuspid regurgitation velocity   2.9  m / s ) . in the initiation phase of the study , after the initiation phase those qol questionnaires were used to form individual qol regression lines in order to divide patients into either a decreased or non - decreased qol group . relevant improvement or decrease of qol was defined as more than two points change during the initiation phase . baseline ( t0 ) was defined as the start of follow - up to determine survival , which was 2 years after the initiation phase in each patient . according to the treatment protocol , patients were evaluated with clinical examination , determination of functional class , 6-min walk distance ( 6-mwd ) , echocardiography , laboratory tests ( including n - terminal pro - brain natriuretic peptide ( nt - pro - bnp ) ) and quality of life questionnaires . these tests were all conducted 24 , 21 , 18 , 15 and 12 months before t0 and at t0 , apart from echocardiography which was performed twice a year . quality of life was evaluated using the 36-item short form health survey ( sf36 ) , a well - documented , widely used and validated , self - administered qol scoring system . it incorporated both a physical and mental component summary ( pcs and mcs ) , thus reflecting physical and mental health . the qol questionnaires were filled out by the patient or , in case of down s syndrome , the patient s parent or guardian . survival and in case of death , time and causes of death during follow - up were obtained from the participating hospitals until march 2014 . doppler echocardiography ( vivid 7 general electric , usa ) was performed to evaluate right ventricular function , using tricuspid annular plane systolic excursion ( tapse ) from m - mode recordings . descriptive data were presented as mean    sd if normally distributed or median with iqr , as appropriate . the change of continuous variables was evaluated using a two - tailed paired t test . independent sample t test or mann - whitney u test was used for comparison of continuous variables between two groups . log - rank test was performed to determine significant differences in mortality rate between the two groups . all reported p values are two - sided , and values of p  <  0.05 were considered significant . statistical analysis was performed with spss 20.0 ( ibm corp , armonk , ny ) . since this study focused on shift in qol , only data from patients who returned more than one questionnaire were used in the final analysis . this was a prospective multicentre observational study of adult patients with pah associated with chd , including patients with down s syndrome [ 17 , 18 ] , referred for pah - specific therapy between january 2005 and may 2013 . the current qol study was part of an ongoing non - randomised trial on pah - specific therapy in pah - chd patients . patients with all kinds of structural heart defects , including closed defects , could be enrolled . pah was defined upon the echocardiographic pah probability ( tricuspid regurgitation velocity   2.9  m / s ) . in the initiation phase of the study , pah - specific therapy was started according to a standardised protocol . after the initiation phase those qol questionnaires were used to form individual qol regression lines in order to divide patients into either a decreased or non - decreased qol group . relevant improvement or decrease of qol was defined as more than two points change during the initiation phase . baseline ( t0 ) was defined as the start of follow - up to determine survival , which was 2 years after the initiation phase in each patient . according to the treatment protocol , patients were evaluated with clinical examination , determination of functional class , 6-min walk distance ( 6-mwd ) , echocardiography , laboratory tests ( including n - terminal pro - brain natriuretic peptide ( nt - pro - bnp ) ) and quality of life questionnaires . these tests were all conducted 24 , 21 , 18 , 15 and 12 months before t0 and at t0 , apart from echocardiography which was performed twice a year . quality of life was evaluated using the 36-item short form health survey ( sf36 ) , a well - documented , widely used and validated , self - administered qol scoring system . it incorporated both a physical and mental component summary ( pcs and mcs ) , thus reflecting physical and mental health . the qol questionnaires were filled out by the patient or , in case of down s syndrome , the patient s parent or guardian . survival and in case of death , time and causes of death during follow - up were obtained from the participating hospitals until march 2014 . doppler echocardiography ( vivid 7 general electric , usa ) was performed to evaluate right ventricular function , using tricuspid annular plane systolic excursion ( tapse ) from m - mode recordings . descriptive data were presented as mean    sd if normally distributed or median with iqr , as appropriate . the change of continuous variables was evaluated using a two - tailed paired t test . independent sample t test or mann - whitney u test was used for comparison of continuous variables between two groups . time to event analysis was performed with kaplan - meier estimates of survival . log - rank test was performed to determine significant differences in mortality rate between the two groups . all reported p values are two - sided , and values of p  <  0.05 were considered significant . statistical analysis was performed with spss 20.0 ( ibm corp , armonk , ny ) . since this study focused on shift in qol , only data from patients who returned more than one questionnaire were used in the final analysis . ninety - one adults ( 42    14 year ) with pah - chd were included ( fig .  1 ) , divided over amsterdam ( 64 ) , one patient refused treatment initiation . in five patients health insurance refused reimbursement of treatment . of these , 61 ( 72  % ) patients returned the first qol questionnaire . baseline characteristics of these 61 patients are described in the supplementary data ( table s1 ) . in the 61 patients returning the first qol questionnaire , no differences in qol were found among those who continued and those who were lost to follow - up , for either the sf36 pcs ( mean values 3535 respectively , p  =  0.930 ) or sf36 mcs ( mean values 5048 respectively , p  =  0.426 ) . in total 39 pah - chd patients ( mean age 42    12 , 44  % male , 49  % down s syndrome ) completed the initiation phase and their data were used for the final analysis.fig . 1flowchart of patient inclusion flowchart of patient inclusion baseline characteristics at t0 are summarised in table  1 . based on their individual sf36 pcs regression lines during the two - year initiation phase ( fig . 2b ) and group 2 of patients without decreased sf36 pcs regression lines ( fig . mean sf36 pcs was 38    12 ( range 10.9658.32 , n  =  39 ) , which is more than one sd lower than the general population . sf36 mcs was 49    13 ( 22.9666.79 , n  =  39 ) , which closely resembles the mean score of the general population . the two groups , based on either decreased or non - decreased sf36 pcs , were well balanced with respect to most clinical characteristics . however , patients with decreased sf36 pcs had a lower baseline 6-mwd ( p  =  0.009 ) and new york heart association ( nyha ) class ( p  =  0.006 ) , compared with patients without a decrease . in contrast , no relation was found between change in sf36 pcs and change in 6-mwd ( r  =  0.12 , p  =  0.468).fig . 2 
 a individual sf36 pcs regression lines of 39 pah - chd patients . b decreased sf36 pcs regression lines , 13 patients . all qol measurements were recorded in the initiation phase after the start of pah - specific standardised therapy . the thick lines represent the mean regression linestable 1baseline characteristics at t0variablesall patientsgroup 1 ( decreased qol)group 2 ( non - decreased qol ) 
 p 
 number391326age , mean    sd ( years)42    1243    1042    130.929male , n ( % ) 17 ( 44)7 ( 54)10 ( 39)0.361down s syndrome , n ( % ) 19 ( 49)8 ( 62)11 ( 42)0.257eisenmenger s syndrome , n ( % ) 35 ( 90)13 ( 100)22 ( 85)0.135body mass index , mean    sd ( kg)24    425    324    40.731nyha class iii or iv , n ( % ) 15 ( 43)9 ( 75)6 ( 26)0.006sf36 pcs , mean    sd38    1231    1141    110.010sf36 mcs , mean    sd49    1348    1350    130.716medication  bosentan , n ( % ) 36 ( 92)13 ( 100)23 ( 89)0.202  diuretics , n ( % ) 15 ( 39)5 ( 39)10 ( 39)1.000cardiac surgery , n ( % ) 8 ( 23)2 ( 17)6 ( 26)0.529  age surgery , median ( range ) ( years)6 ( 166)5 ( 27)8 ( 166)0.643saturation in rest , mean    sd ( % ) 85    686    685 70.651nt - pro - bnp , median ( iqr ) ( ng / l)429 ( 1891197)508 ( 2701011)382 ( 1721263)0.3536-mwd , mean    sd , ( m)385    129311    112422    1230.009tapse , mean    sd , mm19    619    719    50.785spap , mean    sd ( mmhg)93    1798    1790    170.212shunt type  pre tricuspid , n ( % ) 6 ( 15)2 ( 15)4 ( 15 )  post tricuspid , n ( % ) 18 ( 46)5 ( 39)13 ( 50)0.760  complex , n ( % ) 15 ( 39)6 ( 46)9 ( 35 ) 
 sf36 pcs short form health survey of physical health ; sf36 mcs short form health survey of mental health ; sd standard deviation ; iqr interquartile range ; qol quality of life ; 6-mwd six - minute walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nt - pro - bnp n - terminal pro - brain natriuretic peptide ; nyha functional class new york heart association functional class 
 complex shunts included atrioventricular septal defect and univentricular heart 
 a individual sf36 pcs regression lines of 39 pah - chd patients . all qol measurements were recorded in the initiation phase after the start of pah - specific standardised therapy . the thick lines represent the mean regression lines baseline characteristics at t0 
 sf36 pcs short form health survey of physical health ; sf36 mcs short form health survey of mental health ; sd standard deviation ; iqr interquartile range ; qol quality of life ; 6-mwd six - minute walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nt - pro - bnp n - terminal pro - brain natriuretic peptide ; nyha functional class new york heart association functional class 
 complex shunts included atrioventricular septal defect and univentricular heart the 39 patients who finished the initiation phase completed 131 questionnaires ( median 4 , range 25 ) . in 13 patents the sf36 pcs decreased by a mean of ten points ( mean values 3626 , p  =  0.006 ) . in the 26 patients without a decrease , qol improved in 20 patients ( mean values 3647 , p  =  0.006 ) and remained stable in 6 ( mean values 3133 , p  =  0.344 ) . decrease in sf36 pcs was equally distributed in patients with ( 53  % ) and without ( 40  % ) down s syndrome ( p  =  0.429 ) . the effect size of decrease was similar in both groups ( mean differences 5.3 and 5.1 , respectively ) . 3variability plot showing median , 25 and 75  % values of qol scores during the initiation phase . a variability of sf36 physical component summary scores . b variability of sf36 mental component summary scores variability plot showing median , 25 and 75  % values of qol scores during the initiation phase . b variability of sf36 mental component summary scores during a median follow - up of 4.5 ( range 0.36.4 ) years , total all - cause mortality was 31  % ( 12 deaths ) . two ( 10  % ) patients died in the non - decreased and ten ( 56  % ) in the decreased qol group ( p  =  0.002 ) . causes of death were right - sided heart failure ( n  =  7 ) , sudden cardiac death ( n  =  2 ) , sepsis ( n  =  1 ) and unknown ( n  =  2 ) . seven out of 19 patients with down s syndrome died during follow - up compared with 5 out of 20 non - down patients ( p  =  0.423 ) . using univariate cox regression analysis , the significant determinants of mortality were age , nyha classification , nt - pro - bnp , 6-mwd and decrease in sf36 pcs ( table  2 ) . patients with a decrease in sf36 pcs had a 5-year survival of 29  % compared with 74  % in those without a decrease in sf36 pcs ( fig . 4).fig . 4kaplan - meier survival curve between pah - chd patients with decreased and non - decreased sf36 pcs , 2 years after initiation of pah - specific therapytable 2determinants of survival at t0 in 39 pah - chd patientsunivariate analysishr95  % ci 
 p 
 male gender1.110.363.440.863age , per 5 years1.291.061.560.009saturation at rest1.020.941.120.594ferritin ( g / l)0.990.971.020.613nyha 3 or 44.501.3015.560.018nt - pro - bnp , per 500  ng / l1.151.041.270.0056-mwd , per 10  m0.920.870.970.003spap ( mmhg)1.010.971.040.673tapse ( mm)0.890.781.020.097qol pcs0.980.911.050.534qol mcs1.010.951.070.768decreasing saturation at rest0.930.283.050.898decreasing nt - pro - bnp0.910.273.040.874decreasing nyha class0.450.102.060.304decreasing 6-mwd2.780.859.160.092decreasing spap0.680.222.150.511decreasing tapse2.820.7510.640.126decreasing qol pcs3.381.0311.120.045decreasing qol mcs1.610.435.950.478 
 hr hazard ratio ; qol quality of life ; pcs physical summary score ; mcs mental summary score ; 6-mwd 6-min walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nyha functional class new york heart association functional class ; nt - pro - bnp n - terminal pro - brain natriuretic peptide kaplan - meier survival curve between pah - chd patients with decreased and non - decreased sf36 pcs , 2 years after initiation of pah - specific therapy determinants of survival at t0 in 39 pah - chd patients 
 hr hazard ratio ; qol quality of life ; pcs physical summary score ; mcs mental summary score ; 6-mwd 6-min walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nyha functional class new york heart association functional class ; nt - pro - bnp n - terminal pro - brain natriuretic peptide ninety - one adults ( 42    14 year ) with pah - chd were included ( fig .  1 ) , divided over amsterdam ( 64 ) , one patient refused treatment initiation . in five patients health insurance refused reimbursement of treatment . of these , 61 ( 72  % ) patients returned the first qol questionnaire . baseline characteristics of these 61 patients are described in the supplementary data ( table s1 ) . in the 61 patients returning the first qol questionnaire , no differences in qol were found among those who continued and those who were lost to follow - up , for either the sf36 pcs ( mean values 3535 respectively , p  =  0.930 ) or sf36 mcs ( mean values 5048 respectively , p  =  0.426 ) . in total 39 pah - chd patients ( mean age 42    12 , 44  % male , 49  % down s syndrome ) completed the initiation phase and their data were used for the final analysis.fig . 1flowchart of patient inclusion flowchart of patient inclusion baseline characteristics at t0 are summarised in table  1 . based on their individual sf36 pcs regression lines during the two - year initiation phase ( fig . 2b ) and group 2 of patients without decreased sf36 pcs regression lines ( fig . mean sf36 pcs was 38    12 ( range 10.9658.32 , n  =  39 ) , which is more than one sd lower than the general population . sf36 mcs was 49    13 ( 22.9666.79 , n  =  39 ) , which closely resembles the mean score of the general population . the two groups , based on either decreased or non - decreased sf36 pcs , were well balanced with respect to most clinical characteristics . however , patients with decreased sf36 pcs had a lower baseline 6-mwd ( p  =  0.009 ) and new york heart association ( nyha ) class ( p  =  0.006 ) , compared with patients without a decrease . in contrast , no relation was found between change in sf36 pcs and change in 6-mwd ( r  =  0.12 , p  =  0.468).fig . 2 
 a individual sf36 pcs regression lines of 39 pah - chd patients . b decreased sf36 pcs regression lines , 13 patients . all qol measurements were recorded in the initiation phase after the start of pah - specific standardised therapy . the thick lines represent the mean regression linestable 1baseline characteristics at t0variablesall patientsgroup 1 ( decreased qol)group 2 ( non - decreased qol ) 
 p 
 number391326age , mean    sd ( years)42    1243    1042    130.929male , n ( % ) 17 ( 44)7 ( 54)10 ( 39)0.361down s syndrome , n ( % ) 19 ( 49)8 ( 62)11 ( 42)0.257eisenmenger s syndrome , n ( % ) 35 ( 90)13 ( 100)22 ( 85)0.135body mass index , mean    sd ( kg)24    425    324    40.731nyha class iii or iv , n ( % ) 15 ( 43)9 ( 75)6 ( 26)0.006sf36 pcs , mean    sd38    1231    1141    110.010sf36 mcs , mean    sd49    1348    1350    130.716medication  bosentan , n ( % ) 36 ( 92)13 ( 100)23 ( 89)0.202  diuretics , n ( % ) 15 ( 39)5 ( 39)10 ( 39)1.000cardiac surgery , n ( % ) 8 ( 23)2 ( 17)6 ( 26)0.529  age surgery , median ( range ) ( years)6 ( 166)5 ( 27)8 ( 166)0.643saturation in rest , mean    sd ( % ) 85    686    685 70.651nt - pro - bnp , median ( iqr ) ( ng / l)429 ( 1891197)508 ( 2701011)382 ( 1721263)0.3536-mwd , mean    sd , ( m)385    129311    112422    1230.009tapse , mean    sd , mm19    619    719    50.785spap , mean    sd ( mmhg)93    1798    1790    170.212shunt type  pre tricuspid , n ( % ) 6 ( 15)2 ( 15)4 ( 15 )  post tricuspid , n ( % ) 18 ( 46)5 ( 39)13 ( 50)0.760  complex , n ( % ) 15 ( 39)6 ( 46)9 ( 35 ) 
 sf36 pcs short form health survey of physical health ; sf36 mcs short form health survey of mental health ; sd standard deviation ; iqr interquartile range ; qol quality of life ; 6-mwd six - minute walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nt - pro - bnp n - terminal pro - brain natriuretic peptide ; nyha functional class new york heart association functional class 
 complex shunts included atrioventricular septal defect and univentricular heart 
 a individual sf36 pcs regression lines of 39 pah - chd patients . all qol measurements were recorded in the initiation phase after the start of pah - specific standardised therapy . the thick lines represent the mean regression lines baseline characteristics at t0 
 sf36 pcs short form health survey of physical health ; sf36 mcs short form health survey of mental health ; sd standard deviation ; iqr interquartile range ; qol quality of life ; 6-mwd six - minute walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nt - pro - bnp n - terminal pro - brain natriuretic peptide ; nyha functional class new york heart association functional class 
 complex shunts included atrioventricular septal defect and univentricular heart the 39 patients who finished the initiation phase completed 131 questionnaires ( median 4 , range 25 ) . in 13 patents the sf36 pcs decreased by a mean of ten points ( mean values 3626 , p  =  0.006 ) . in the 26 patients without a decrease , qol improved in 20 patients ( mean values 3647 , p  =  0.006 ) and remained stable in 6 ( mean values 3133 , p  =  0.344 ) . decrease in sf36 pcs was equally distributed in patients with ( 53  % ) and without ( 40  % ) down s syndrome ( p  =  0.429 ) . the effect size of decrease was similar in both groups ( mean differences 5.3 and 5.1 , respectively ) . 3variability plot showing median , 25 and 75  % values of qol scores during the initiation phase . a variability of sf36 physical component summary scores . b variability of sf36 mental component summary scores variability plot showing median , 25 and 75  % values of qol scores during the initiation phase . during a median follow - up of 4.5 ( range 0.36.4 ) years , total all - cause mortality was 31  % ( 12 deaths ) . two ( 10  % ) patients died in the non - decreased and ten ( 56  % ) in the decreased qol group ( p  =  0.002 ) . causes of death were right - sided heart failure ( n  =  7 ) , sudden cardiac death ( n  =  2 ) , sepsis ( n  =  1 ) and unknown ( n  =  2 ) . five - year mortality for all patients was 18  % . seven out of 19 patients with down s syndrome died during follow - up compared with 5 out of 20 non - down patients ( p  =  0.423 ) . using univariate cox regression analysis , the significant determinants of mortality were age , nyha classification , nt - pro - bnp , 6-mwd and decrease in sf36 pcs ( table  2 ) . patients with a decrease in sf36 pcs had a 5-year survival of 29  % compared with 74  % in those without a decrease in sf36 pcs ( fig . 4).fig . 4kaplan - meier survival curve between pah - chd patients with decreased and non - decreased sf36 pcs , 2 years after initiation of pah - specific therapytable 2determinants of survival at t0 in 39 pah - chd patientsunivariate analysishr95  % ci 
 p 
 male gender1.110.363.440.863age , per 5 years1.291.061.560.009saturation at rest1.020.941.120.594ferritin ( g / l)0.990.971.020.613nyha 3 or 44.501.3015.560.018nt - pro - bnp , per 500  ng / l1.151.041.270.0056-mwd , per 10  m0.920.870.970.003spap ( mmhg)1.010.971.040.673tapse ( mm)0.890.781.020.097qol pcs0.980.911.050.534qol mcs1.010.951.070.768decreasing saturation at rest0.930.283.050.898decreasing nt - pro - bnp0.910.273.040.874decreasing nyha class0.450.102.060.304decreasing 6-mwd2.780.859.160.092decreasing spap0.680.222.150.511decreasing tapse2.820.7510.640.126decreasing qol pcs3.381.0311.120.045decreasing qol mcs1.610.435.950.478 
 hr hazard ratio ; qol quality of life ; pcs physical summary score ; mcs mental summary score ; 6-mwd 6-min walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nyha functional class new york heart association functional class ; nt - pro - bnp n - terminal pro - brain natriuretic peptide kaplan - meier survival curve between pah - chd patients with decreased and non - decreased sf36 pcs , 2 years after initiation of pah - specific therapy determinants of survival at t0 in 39 pah - chd patients 
 hr hazard ratio ; qol quality of life ; pcs physical summary score ; mcs mental summary score ; 6-mwd 6-min walk distance ; spap systolic pulmonary artery pressure ; tapse tricuspid annular plane systolic excursion ; nyha functional class new york heart association functional class ; nt - pro - bnp n - terminal pro - brain natriuretic peptide the current study shows , for the first time , that a decrease in qol on the physical component of the sf36 during the initiation phase of pah - specific therapy in adult pah - chd patients is associated with late mortality . patients with a decrease in sf36 pcs had a 5-year survival of 29  % compared with 74  % in those without a decrease in sf36 pcs . our finding is in line with previous studies demonstrating an association between qol and mortality , in healthy people   and in patients with acquired heart disease [ 11 , 12 , 20 ] . the above - mentioned studies used single instead of serial qol measurements . in 2013 , proposed that serial follow - up on qol could be of more value than single measurements . they identified psychosocial determinants of baseline and serial qol [ 22 , 23 ] , analysed associations between qol and exercise capacity over time   and provided insight into the longitudinal course of qol . we , however , demonstrate that assessing qol with serial follow - up provides useful information about late mortality , suggesting that serial follow - up may be a robust guide to clinical management in chd patients . the use of patient - reported outcomes such as qol instruments in clinical practice could help to screen for functional problems , to monitor disease progression or treatment effect , to stratify patients according to mortality risk and to guide clinical management . in order to implement serial qol follow - up in clinical practice , its predictive value for mortality has to be weighed against traditional determinants of mortality in pah - chd . unfortunately , multivariate regression analysis could not be performed in our study due to the small number of events . however , despite our number of events , decrease in qol was significantly associated with mortality , making it a promising determinant . it is possible that physical quality of life is a proxy for disease severity . in accordance , patients with decreased qol on the physical component of the sf36 in our study had a lower 6-mwd and worse nyha class implying more advanced disease . however , if decrease in qol were merely a proxy for disease severity , one would expect baseline sf36 pcs to predict mortality as well and this was not the case . given the results described above , we suggest the use of serial qol follow - up in clinical practice to determine a patient s mortality . the relationship between decrease in qol and late mortality in adult pah - chd patients , as shown in our study , emphasises the importance of screening for decrease in qol since periodical assessment could facilitate an early recognition of disease progression . the use of knowledge from other areas of heart disease can be important for this task . in patients with acquired heart failure , baseline qol they used minnesota qol questionnaires for up to 5 years with extended follow - up to 6 years for prognosis assessment . during this period 457 deaths were recorded . a decrease in qol ( score deterioration of   10  % ) was associated with impaired 12-month survival ( hr 1.012 , 95  % ci 1.0061.018 , p  <  0.001 ) . on top of qol serving as a determinant for mortality , three other studies reported that stimulation of physical activity has shown to be effective for improving qol , as well as mortality [ 1416 ] . it might be interesting for future studies in pah - chd patients to evaluate whether an improvement of qol influences survival . quality of life questionnaires have not been properly validated in patients with down s syndrome . to address this problem and increase their validity , self - reports are impossible in these patients , even though the sf36 has not been validated for proxy report , it is the most appropriate way to evaluate qol in down s syndrome patients . this approach has yielded favourable results in earlier studies [ 3 , 5 , 26 ] and makes sure new scientific insights are also gained for patients with down s syndrome . in this study , decrease in sf36 pcs was equally distributed and had a similar effect size for both down and non - down patients . however , further research is crucial to determine the value of questionnaires by proxy reports . although our study comprises the largest dutch cohort of pah - chd patients , we were unfortunately unable to perform multivariate regression analysis due to the number of events . finally , invasive haemodynamics are recommended in the guidelines for the diagnosis of pah [ 27 , 28 ] . however , echocardiography is an adequate non - invasive modality in patients with evident diagnosis of pah [ 29 , 30 ] in patients with chd . due to the higher complication risk in patients with pah - chd cardiac catheterisation was not routinely performed in these patients , but only if the diagnosis of pah was not clearly evident at echocardiography . the current study shows , for the first time , that a decrease in qol on the physical component of the sf36 during the initiation phase of pah - specific therapy in adult pah - chd patients is associated with late mortality . patients with a decrease in sf36 pcs had a 5-year survival of 29  % compared with 74  % in those without a decrease in sf36 pcs . our finding is in line with previous studies demonstrating an association between qol and mortality , in healthy people   and in patients with acquired heart disease [ 11 , 12 , 20 ] . the above - mentioned studies used single instead of serial qol measurements . in 2013 , proposed that serial follow - up on qol could be of more value than single measurements . they identified psychosocial determinants of baseline and serial qol [ 22 , 23 ] , analysed associations between qol and exercise capacity over time   and provided insight into the longitudinal course of qol . we , however , demonstrate that assessing qol with serial follow - up provides useful information about late mortality , suggesting that serial follow - up may be a robust guide to clinical management in chd patients . the use of patient - reported outcomes such as qol instruments in clinical practice could help to screen for functional problems , to monitor disease progression or treatment effect , to stratify patients according to mortality risk and to guide clinical management . in order to implement serial qol follow - up in clinical practice , its predictive value for mortality has to be weighed against traditional determinants of mortality in pah - chd . unfortunately , multivariate regression analysis could not be performed in our study due to the small number of events . however , despite our number of events , decrease in qol was significantly associated with mortality , making it a promising determinant . it is possible that physical quality of life is a proxy for disease severity . in accordance , patients with decreased qol on the physical component of the sf36 in our study had a lower 6-mwd and worse nyha class implying more advanced disease . however , if decrease in qol were merely a proxy for disease severity , one would expect baseline sf36 pcs to predict mortality as well and this was not the case . given the results described above , we suggest the use of serial qol follow - up in clinical practice to determine a patient s mortality . the relationship between decrease in qol and late mortality in adult pah - chd patients , as shown in our study , emphasises the importance of screening for decrease in qol since periodical assessment could facilitate an early recognition of disease progression . the use of knowledge from other areas of heart disease can be important for this task . in patients with acquired heart failure , baseline qol they used minnesota qol questionnaires for up to 5 years with extended follow - up to 6 years for prognosis assessment . during this period 457 deaths were recorded . a decrease in qol ( score deterioration of   10  % ) was associated with impaired 12-month survival ( hr 1.012 , 95  % ci 1.0061.018 , p  <  0.001 ) . on top of qol serving as a determinant for mortality , three other studies reported that stimulation of physical activity has shown to be effective for improving qol , as well as mortality [ 1416 ] . it might be interesting for future studies in pah - chd patients to evaluate whether an improvement of qol influences survival . quality of life questionnaires have not been properly validated in patients with down s syndrome . to address this problem and increase their validity , since self - reports are impossible in these patients , even though the sf36 has not been validated for proxy report , it is the most appropriate way to evaluate qol in down s syndrome patients . this approach has yielded favourable results in earlier studies [ 3 , 5 , 26 ] and makes sure new scientific insights are also gained for patients with down s syndrome . in this study , decrease in sf36 pcs was equally distributed and had a similar effect size for both down and non - down patients . however , further research is crucial to determine the value of questionnaires by proxy reports . although our study comprises the largest dutch cohort of pah - chd patients , we were unfortunately unable to perform multivariate regression analysis due to the number of events . finally , invasive haemodynamics are recommended in the guidelines for the diagnosis of pah [ 27 , 28 ] . however , echocardiography is an adequate non - invasive modality in patients with evident diagnosis of pah [ 29 , 30 ] in patients with chd . due to the higher complication risk in patients with pah - chd cardiac catheterisation was not routinely performed in these patients , but only if the diagnosis of pah was not clearly evident at echocardiography . a decrease in qol on the physical component of the sf36 after the initiation of pah - specific therapy in adult pah - chd patients predicts mortality . patients with a decrease in sf36 pcs during the initiation phase have a 5-year survival of 29  % compared with 74  % in those without a decrease in sf36 pcs . periodical assessment of quality of life in pah - chd patients could facilitate early recognition of disease progression . based on the association between qol and mortality , it might be interesting for future studies in pah - chd patients to evaluate whether interventions to improve qol might influence survival .
backgrounddecrease in quality of life ( qol ) in left - sided heart failure precedes poor survival , which can be reversed with exercise training . 
 we investigated whether qol is associated with mortality in pulmonary arterial hypertension due to congenital heart disease ( pah - chd ) patients.methodsin this observational study , pah - chd adults referred for pah - specific therapy were included . 
 qol surveys ( sf36 ) were recorded during 2 years of therapy . based on shift in sf36 scores during this period , 
 patients had either decreased or non - decreased qol . 
 subsequently , the patients were followed for mortality.resultsthirty-nine pah - chd patients ( mean age 42 , 44  % male , 49  % down s syndrome ) were analysed . 
 following pah - specific therapy , sf36 physical component summary ( pcs ) decreased in 13 ( 3531 points , p  =  0.001 ) and showed no decrease in 26 patients ( 3443 points , mean values , p  <  0.001 ) . 
 post - initiation phase , median follow - up was 4.5 years , during which 12 deaths occurred ( 31  % ) , 10 ( 56  % ) in the decreased and 2 ( 10  % ) in the non - decreased group ( p  =  0.002 ) . 
 cox regression showed a decrease in sf36 pcs predicted mortality ( hr 3.4 , 95  % ci 1.0311 , p  =  0.045).conclusionsin pah - chd patients , decrease in sf36 pcs following initiation of pah - specific therapy is a determinant of mortality.electronic supplementary materialthe online version of this article ( doi:10.1007/s12471 - 015 - 0666 - 9 ) contains supplementary material , which is available to authorized users .