Qualité de vie des patients porteurs de Cardiopathie

CongénitaleDr Pascal AMEDRO

p-amedro@chu-montpellier.fr

Cardiologie Pédiatrique et Congénitale - CHU de Montpellier - FranceEA 3279 - Département de Santé Publique - Université Aix-Marseille - France

INSERM U1046 - Physiologie et médecine expérimentale du coeur et des vaisseaux - Montpellier - France

!

!

!

!

"#$%&'()!*+%,+-!."/012!32*45.6!.17.80!0/!9466/7/89/!:/194;/!*/04.514/!!<!=><!.?'$('!0#@'$!A&)+(B!=CDEF!"#$GH'--&')!I1.7;/!

7'(&--@J%()J:'&$'!-'!DK!$#?'LM)'!DK<C!

!

1'N!O! C'%! 1'$,#$G)'%! I)+$,#HP#$'%! "(-G&B&%,&H-&$+&)'%! B'%! ;+)B&#H+GP&'%!;#$QR$&G+-'%!!DSJD>!7#?'LM)'!DK<C! !A)+$B!5PRTG)'U!V#)B'+(W!!

;P')!"#$%&'()U!!

'%! 1'$,#$G)'%! I)+$,#HP#$'%! "(-G&B&%,&H-&$+&)'! B'%!;+)B&#H+GP&'%!;#$QR$&G+-'%!X(&!%'!G&'$B)#$G! -'%!DS!'G!D>!$#?'LM)'!H)#,P+&$%U!$#(%! +?#$%! -'! H-+&%&)! B'! ?#(%! +B)'%%')! -'%! B')$&Y)'%! &$N#)L+G&#$%! ,#$,')$+$G!?#G)'!%RZ#()![!V#)B'+(W\!!4$N#)L+G&#$%!%,&'$G&N&X('%!!7#(%! ?#(%! )+HH'-#$%! X('! ?#(%! &$G')?'$']! '$! X(+-&GR! B^#)+G'()! -#)%! B'! -+!%'%%&#$!O!!6'%!,#$QR$&G+(W![!-^TQ'!+B(-G'!!_(&!%'!BR)#(-')+!-'!"'),)'B&!DS!7#?'LM)'!DK<CU!B'!<KPKK![!<DPKK\!

!9#G)'!,#LL($&,+G&#$!O!_(+-&GR!B'!?&'!B'%!A8;3!9#(%! B&%H#%')']! DK!L&$(G'%! `! <K!L&$(G'%! B'!X('%G&#$%\!7#(%!?#(%!)'L'),&#$%!B'!M&'$!?#(-#&)!)'%H',G')!-'%!G'LH%!B'!H+)#-'!H#()!-'!M#$!BR)#(-'L'$G!B(!;#$Q)Y%\!!0+$%! -'! %#(,&! B'! Q+)+$G&)! -+!L'&--'()'! X(+-&GR! B'! H)R%'$G+G&#$! H#%%&M-'U! $#(%!?#(%!H)&#$%!B'!?#(%!H)R%'$G')!'$!%+--'!B'!*)'?&'a!+(!H-(%!G+)B!D!P'()'%!+?+$G!?#G)'!H)R%'$G+G&#$\!!7#(%! ?#(%! B'L+$B#$%! B'! H)R?#&)! ?#G)'! H)R%'$G+G&#$! '$)'Q&%G)R'! %()! ($'! ,-R!8:V\!!

1

La complexité du concept de QdV

• Pas de norme ISO «qualité de vie»!

• Peut-on s’accorder sur une définition opérationnelle, standardisée, explicite et permettant une mesure quantitative ?

• Chacun n’aurait-il pas sa définition personnelle ?

• Comment évaluer une donnée subjective ?

• Peut-on quantifier le qualitatif ?

• Qui est l’expert?

• Le chercheur en épidémiologie?

• Le patient?

• Le proche du patient?

• Le clinicien référent? 2

Qu’est-ce la Qualité de Vie (QdV)?

• La qualité de vie recouvre tous les secteurs de la vie :

• État fonctionnel : aptitudes physiques, capacités intellectuelles, réussite scolaire et sociale, qualité des relations sociales, maturité relationnelle et affective…

• Niveau de développement : compétences et performances, autonomie…

• Épanouissement psychologique : personnalité, tempérament, vulnérabilité, rapport à soi et au monde…

• Conditions de vie : matérielles, sociales…

3

• Avant, évaluation des maladies chroniques uniquement par les variables classiques de morbi-mortalité :

• Taux de mortalité,

• Complications péri-opératoires,

• Durées de séjour à l’hôpital,

• Survie actuarielle,

• Scores quantitatifs ou semi-quantitatifs de sévérité divers (NYHA, ...).

• Aujourd’hui, l’évaluation de la qualité de vie des malades chroniques est indispensable :

• Elle doit être associée à la mesure des variables quantitatives classiques de morbi-mortalité,

• Elle est un outil d’aide à la décision médicale,

• Elle participe à l’évaluation des pratiques médicales,

• Santé publique : « Plan 2007-2011 pour l’amélioration de la qualité de vie des patients atteints de maladies chroniques ».

4

Comment évaluer la QdV?

• Avec des questionnaires validés (validation linguistique et psychométrique)

• Mais avant : un quiproquo à lever !

• Pour les cliniciens QdV de leur patient = reflet de leur état fonctionnel.

• Pour le patient et les chercheurs en épidémiologie, la QdV = état de satisfaction globale de sa vie dans son ensemble

5

Questionnaires de QdV

• Générique adulte : SF-36

• Spécifique adulte : Camphor (HTAP)

• Générique enfants/parents : PedsQL, Kidscreen

• Spécifique enfant : module cardiaque PedsQL

• Choisir un questionnaire validé dans la culture du pays concerné +++

6

Questionnaires de QDV utilisés dans les publications de cardiologie congénitale Questionnaires de QDV utilisés dans les publications de cardiologie congénitale Questionnaires de QDV utilisés dans les publications de cardiologie congénitale Questionnaires de QDV utilisés dans les publications de cardiologie congénitale Questionnaires de QDV utilisés dans les publications de cardiologie congénitale Questionnaires de QDV utilisés dans les publications de cardiologie congénitale

Questionnaires Module général en Français Module cardiaque Enfant Adulte Parent

TNO-AZL Non Oui 8-15 ans Oui oui

PedsQLOui

(sans validation psychométrique en Français)

Oui(pas en Français) 2-18 ans Non Oui

ConQL Non Oui (anglais) 8-16 ans Non Non

LQ-Kid Non Non 8-16 ans Non Oui

WHOL QOL Non Non Non oui Non

SF 36 Oui Non non Oui Non

Lindström Non Non Non Oui Non

Göteberg Non Non Non Oui Non

CF 87 Non Non >11 ans Oui Non

Duke Oui Oui Non Oui Non7

Conduire une étude de QdV : les pièges à éviter

• Biais d’information

• Enquête téléphonique

• Questionnaire rempli en face du médecin référent

• Biais de confusion = autres facteurs qui influencent la QdV

• dépression (Rose et al. 111 ACHD 21-45 ans. QoL Res 2005)

• anxiété : mauvais moment (hospitalisation, annonce)

• autre maladie chronique

• Biais de sélection

• quid des non répondeurs aux questionnaires?

• quid des malades « non graves » ou guéris : souvent oubliés

• Ne pas avoir de population témoin représentative

• Ex : comparaison aux normes USA du SF36

8

Un score de QdV reflète-t-il l’état fonctionnel d’un ACHD?• OUI !!!

• Les cardiologues ont démontré la bonne corrélation entre la dimension physique des questionnaire QdV et sévérité de l’insuffisance cardiaque chronique de l’adulte

• Les rares études ayant corrélé QdV et sévérité de la CC confirment cela également :

• bonne corrélation entre VO2 et dimensions physique du SF36 (n=149 ACHD 14-60 ans, Hager et al. Heart 2005).

• score physique QdV d’une CC complexe altéré vs pop générale (n=78 ACHD 18-32 ans type Fontan, Mustard, Senning, Kamphuis et al. Heart 2002)

• dimension physique QdV TGV simple > TGV complexe (n= 306 TGV Culbert Circulation 2003)

9

La VO2 et la QdV : le binôme idéal pour évaluer les ACHD?

80+30, and 78+25% of predicted peakVO2, respectively).There were also significant differences in VE/VCO2 slope (P,0.001, on one-way ANOVA) with the highest values found inpatients with Eisenmenger syndrome and complex heart disease(72+55 and 52+19, respectively) and the lowest values inpatients with TGA after arterial switch and corrected aortic coarc-tation (30+ 5 and 30+ 8, respectively) (Table 2). Table 1 informs

about the distribution of peak VO2 and VE/VCO2 slope (mean andstandard deviation) in published studies.

In most diagnostic subgroups men achieved significantly higherpeak VO2-values than women (Table 3). Therefore, when lookingat the peak VO2 levels required to perform various activities(such as movement, sporting activities, occupation, or home activ-ities), more women than men were found to have an exercise

Figure 1 Peak oxygen uptake (peak VO2) data expressed as % of predicted value. Histograms represent data from our own institution. Thedensity lines above histograms and the numbers to the right of the graph relate to all patients with a given diagnosis. The numbers above thedensity lines indicate %peak VO2 values for the 10, 25, 50, 75 and 90th centile. ASD, atrial septal defect; ccTGA, congenitally corrected TGA;CoA, coarctation of aorta; Complex, complex congenital heart disease (including univentricular hearts); Ebstein, Ebstein anomaly; Eisenmenger,Eisenmenger syndrome; Fontan, patients after Fontan palliation; TGA, transposition of the great arterial; ToF, tetralogy of Fallot; Valvular, mixedcollective of patients with congenital valvular heart disease; VSD, ventricular septal defect.

A. Kempny et al.Page 4 of 11

by Geetika Sapra on January 17, 2012

http://eurheartj.oxfordjournals.org/D

ownloaded from

n= 4415 ACHD avec VO2 Kempny et al, European Heart Journal 201110

Corrélation entre qualité de vie et épreuve d’effort

• OMS 1980 : concept de WOOD : l’EE reflète mieux la QdV et le handicap social qu’un examen de repos

• VO2 max et pente VE/VCO2 sont corrélées à la classe NYHA et à la QdV

• Giardini et al. Natural history of exercise capacity after the Fontan operation: a longitudinal study. Ann Thorac Surg 2008.

• Mancini et al. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991.

• Ponikowski et al. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation 2001.

11

Retentissement de la cardiopathie sur la vie quotidienne : rôle de la VO2

• ACHD sans emploi => 5 X plus que population générale

• inactivité non corrélée à la sévérité de la cardiopathie

• mauvaise estimation du véritable retentissement fonctionnel de la cardiopathie : par les médecins (généralistes, médecins du travail), par la MDPH, par le patient, par son entourage...

• choix potentiellement inadapté des études, de la formation professionnelle, du métier.

• VO2 est la 1ère étape vers un programme de réhabilitation à l’effort : perspectives +++

12

Retentissement de la cardiopathie sur la vie quotidienne : rôle de la VO2

• Calcul des dépenses énergétiques en fonction d’une liste d’activités => «The Compendium of Physical Activities» Ainsworth BE et al. (2011). The Compendium of Physical Activities Tracking Guide. Arizona State University, USA : https://sites.google.com/site/compendiumofphysicalactivities/

• 1 MET (metabolic equivalent of task) = 3,5ml/kg/min

• ACHD : VO2 au SV1 = 0,7 x VO2max (Kempny et al. EHJ 2011)

VO2 idéale pour maintenir activité en dessous du seuil ventilatoire : nombre de METS x 3,5 x 0,7

13

te

14

QdV : critère de jugement dans l’HTAP associée aux CC?

From Chen et al. Proc Am Thorac Soc 2008

such as dyspnea, or broader concerns, such as ‘‘quality of life.’’As such, PROs are unique in that they directly assess benefits tothe patient for which no adequate observable or physicalmeasures exist. Furthermore, PROs are often designed to capturethe patient’s perspective, thereby adding another dimension toour understanding of a patient’s response to treatment thatcannot be extrapolated from physiologic or clinical endpoints.Finally, PROs are relatively quick and easy to administer, andprovide a more formal assessment than outcomes that requirea clinical interpretation of the patient’s status. Figure 1 depictsthe relationships among various types of endpoints in PAH, andthe context in which PRO measures are frequently used.

TYPES OF PRO MEASURES USED IN PAH

The choice of PRO measure depends on its intended purpose.As shown in Figure 1, PROs in PAH are commonly used tomeasure symptoms, functional status, or HRQoL. Instrumentsdesigned to measure symptoms often consist of single-itemscales, for example the BDI (6). Such rating scales typicallyfocus on the measurement of a defined construct, the interpre-tation of which is usually straightforward (e.g., from no short-ness of breath to severe dyspnea). Consequently, such measuresgenerally do not require the level of conceptual grounding andpsychometric validation expected of more sophisticated healthstatus instruments.

Functional status differs from symptoms in that it refers tothe extent to which symptoms interfere with a patient’s abilityto perform certain tasks or activities (7). Instruments used toassess functional status include a wide variety of measures. Theycan range from single-item scales similar to those used to ratesymptoms, for example the modified Medical Research Council[MRC] scale) (11), to more complex measures that closelyresemble HRQoL instruments. Measures of functional statusextend beyond the determination of exercise capacity alone inthat they incorporate an individual’s ability to perform func-tional activities, as opposed to merely how far a person can walkin 6 minutes.

The concept of HRQoL encompasses that of both symptomsand functional status (12). In principle, HRQoL instruments aredesigned to capture not only the level of impairment, but alsothe impact of that impairment on an individual’s perceivedphysical, psychological, and social well-being (2). HRQoL istherefore a multidimensional construct by definition. MostHRQoL instruments are composed of multiple domains; how-ever, instruments vary in both scope and content. Some inves-tigators distinguish measures of ‘‘health status’’ from true‘‘quality of life’’ instruments, which take into account thepatient’s own expectations or internal standards (5, 13). To theextent that such instruments reflect those aspects of life valued

most by patients, each may provide further insight into thespecific pathways by which PAH leads to HRQoL impairment.

VALIDATION OF HRQOL AND PRO MEASURES

In general, physicians and clinical investigators will agree thatHRQoL is important to assess. In everyday clinical practice,physicians often inquire in an informal manner about HRQoLto determine whether a patient with PAH is benefiting fromtherapy. In clinical trials, however, concern regarding the use ofHRQoL as an endpoint centers not on the issue of relevance,but on whether the instruments used to measure it are reliable,valid, and responsive to the effects of treatment (14). Instru-ments must also be interpretable insofar as they must provideresults that represent a meaningful change to the patient. In2006, the United States Food and Drug Administration (FDA)released a draft guidance document for industry on the appro-priate development and use of PRO measures in medicalproduct development (4). The process of instrument develop-ment and validation represents a highly specialized disciplinethat is beyond the scope of this review, and has been describedwell by others (15). Table 1 provides a brief overview of themethods commonly used to assess the psychometric adequacyof HRQoL and PRO measures.

INSTRUMENTS USED TO ASSESS HRQOL IN PAH

Until a few years ago, very little was known about HRQoLimpairment in PAH. Driven by expanding therapeutic optionsand the ability to focus on endpoints beyond survival, anincreasing number of studies have begun to shed light on thispreviously neglected area of research. Instruments used byinvestigators have varied from study to study, in large partdue to the lack of data on the performance of differentmeasures in PAH. As a result, past investigators have had toeither rely on the use of generic instruments or adapt existingmeasures originally developed for related conditions. Table 2provides a summary of the various instruments used in studiesof HRQoL in PAH.

Generic measures, such as the Medical Outcome Study 36-item Short Form Health Survey (SF-36) (16) and the Notting-ham Health Profile (NHP) (17), are advantageous in that theycan be applied across a broad spectrum of disease states—evenhealthy individuals—thereby allowing comparisons with popu-lation norms over multiple domains. Multi-attribute utility mea-sures, such as the EuroQol (EQ-5D) (18) and the AustralianAssessment of Quality of Life (AQoL) (19), also provide amulti-dimensional assessment of general health, but in addition can beused to derive preference-based ‘‘utility’’ scores that can beapplied in economic analyses. Utilities can also be obtained viadirect elicitation (e.g., visual analog scales [VAS], standard

Figure 1. Simplified conceptual model depicting the relationship between different types of endpoints used in studies of pulmonary arterialhypertension.

624 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 5 2008

15

Etude de Qualité de Vie des HTAP associées aux cardiopathies

congénitales• Etude épidémiologique dans les CC-HTAP/M3C Français sur

1 an

• QdV = critère de jugement principal (SF36, CAMPHOR)

• n= 208 adultes et adolescents > 15 ans

• Présentant une HTAP associée à une cardiopathie congénitale

• Critères cliniques et paracliniques classiques

• VO2, VE/VCO2, SV1, ...

• Echelles anxiété dépression

• Données socio-économiques16

INTRODUCTION AND OBJECTIVES

Pulmonary arterial hypertension (PAH) is a severe and frequent (5–10%) complication of congenital heart disease (CHD).1

Nowadays, patients developing PAH associated with CHD (PAH-CHD) are managed in tertiary care PAH-CHD centres, where the introduction of advanced speci!c therapies is expected to improve survival.2

Health-related quality of life (HRQoL) has become an important endpoint in PAH clinical studies, but limited QoL data are available for PAH-CHD patients.3

The objective of the ACHILLE (Adults adolescents Congenital Heart dIsease with puLmonary arteriaL hypertension quality of lifE assessment) study was to assess HRQoL in a large population of patients with PAH-CHD using a generic (SF-36) and a pulmonary hypertension (PH)-speci!c (CAMPHOR) instrument. Factors impacting HRQoL were investigated.

METHODS

Study design Prospective, cross-sectional, observational study Patients enrolled from May 2012 to June 2013 in 14 tertiary care PAH-CHD centres in France

Patients Fifteen years of age or older PAH con!rmed by right heart catheterisation and/or echocardiography PAH-CHD classi!ed according to the Dana Point clinical classi!cation4 as:

– Eisenmenger syndrome – PAH associated with systemic-to-pulmonary shunts – PAH associated with small defects – PAH after corrective cardiac surgery Exclusion criteria:

– Heart transplantation, cardiac surgery without subsequent control, planned corrective heart surgery, recent surgical or intervention catheter procedures (<6 months)

– Patients unable to !ll out the questionnaire

Data collection at inclusion Demographic and clinical data Health-related quality of life questionnaires

– Short form-36 (SF-36v2 Acute, France). 8 domains are assessed These domains are combined to form two higher-order summaries. Each domain and each summary is reported on a scale from 0 to 100. SF-36 scores are normalised to a mean of 50 and standard deviation of 10 based on the normal US population. A higher score indicates better quality of life.

– Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). The CAMPHOR is divided into three separate scales. Scores range 0–25 for the symptom and QoL scales and 0–30 for the functioning scale. A higher score indicates worse QoL.

Anxiety and depression. – Hospital Anxiety and Depression Scale (HADS). A score between 0 and 3 is assigned to

each item. The total scores for depression and for anxiety range between 0 and 21. We considered a HADS anxiety or depression score "8 represented symptoms of anxiety or depression.

Amedro P1, Basquin A2, Gressin V3, Clerson P4, Jaïs X5, Thambo JB6, Bonnet D7

1Hôpital Arnaud de Villeneuve, Montpellier, France; 2CHU Rennes, France; 3Actelion Pharmaceuticals France, Paris, France; 4Interphase Orgamétrie Biostatistics, Roubaix, France; 5Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; 6Hôpital cardiologique du Haut-Lévêque, Bordeaux, France; 7M3C-Necker, Paris, France

Quality of life of patients with pulmonary arterial hypertension associated with congenital heart disease: The multicentre cross-sectional ACHILLE study

Disclosures: This study was sponsored by Actelion Pharmaceuticals France. PA, XJ, JBT and DB received reimbursements, fees, and/or funding from Actelion Pharmaceuticals France. PC provided statistical analysis, funded by Actelion Pharmaceuticals France. VG is a full time employee of Actelion Pharmaceuticals France. DB exerts consultant activities for P!zer, Bayer, Eli Lilly, and GSK. AB reports no con"ict of interest. Acknowledgements: The authors are thankful to the ACHILLE study investigators from M3C-Georges Pompidou European Hospital, Paris (S Cohen, L Iserin, M Ladouceur, O Sanchez, A Legendre); Bicêtre University Hospital, Le Kremlin-Bicêtre (X Jaïs, O Sitbon); Guillaume and René Laennec Hospital, Nantes (P Guérin, L Le Gloan); Louis Pradel Hospital -cardiology/ respiratory diseases- Bron (A Sénéchal, V Cottin, A Sou!, J Traclet, C Khouatra); Côte de Nacre Hospital, Caen (F Lalombarda, E Bergot, P Maragnes); Charles Nicolle Hospital, Rouen (E Barre); University Hospital, Rennes (J-M Schleich); Gabriel-Montpied University Hospital Clermont-Ferrand (C Dauphin, J-R Lusson); M3C-Necker University Hospital, Paris (M Levy); Haut-Lévêque University Hospital, Bordeaux (X Iriart, M de Guillebon); Albert Michallon Hospital, La Tronche (H Bouvaist); Marie Lannelongue Chirurgical centre, Le Plessis Robinson (A Baruteau, V Lambert, M Gouton), France. Medical writing support was provided by Sylvie Ertel PhD (Sundgau Medical Writers, Habsheim, France) and was funded by Actelion Pharmaceuticals Ltd. Poster presented at the European Respiratory Society, 6–10 September 2014, Munich, Germany.

Statistical analysis Characteristics of patients were compared according to the type of CHD or to New York Heart Association (NYHA) functional class (FC) by analysis of variance (ANOVA) for continuous variables and chi-squared or exact Fisher’s test for categorical variables.

Univariate and multivariate regression analyses were performed to identify the covariates impacting the QoL among the following: gender, age per quartile, time since diagnosis of CHD and of PAH, HADS, 6-minute walk distance (6MWD), NYHA FC, at least one hospitalisation due to PAH and/or CHD in the past 12 months, and recent stressful event.

A signi!cance level of p # 0.05 was used.

RESULTS

Population 208 patients were included in the analysis (Table 1).

Table 1. Characteristics at inclusionPatients with PAH-CHD (n = 208)

DemographicsAge, years ± SD (range) 42.6 ± 15.8 (15.1–85.8)Female gender, n (%) 145 (69.7)

Clinical characteristicsAge at PAH diagnosis, years ± SD (range) 25.9 ± 20.3 [0–80.0]Classi!cation of CHD associated with PAH

Eisenmenger syndrome 147 (70.7)PAH with systemic-pulmonary shunt 25 (12.0)PAH with small defects 7 (3.4)PAH after corrective cardiac surgery 29 (13.9)

At least one hospitalisation in the past 12 months*, n (%) 142 (68.3)NYHA FC I: II: III: IV, % 10.6: 48.1: 37.5: 3.96-minute walk distance, m ± SD 431 ± 109 (n = 147)Clinical status stable for the past 3 months, n (%) 184 (86.0)

PAH-speci!c treatments†, n (%)No treatment 49 (23.6)Monotherapy 85 (40.9)Double combination therapy 66 (31.7)Triple combination therapy 8 (3.9)

Values are expressed as mean ± standard deviation unless otherwise speci!ed; *Hospitalisation due to PAH and/or CHD; †Endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, and/or prostanoid. CHD, congenital heart disease; NYHA FC, New York Heart Association functional class; PAH, pulmonary arterial hypertension.

Health-related quality of life Mean SF-36 scores were low compared with the US normalised mean of 50 for all domains (Figure 1) indicating decreased QoL.

Mean CAMPHOR symptom, functioning, and QoL scores among PAH-CHD patients were 8.8 ± 5.6, 8.5 ± 5.0 and 6.7 ± 5.6, respectively.

Hospital anxiety and depression (HADS) Anxiety and depression component scores of the HADS questionnaire were 7.2 ± 3.9 and 4.0 ± 3.7, respectively.

HADS anxiety and depression scores were above 8 (representing symptoms of anxiety or depression) for 64 patients (31.4%) and 19 patients (9.2%), respectively.

Effect of gender, PAH-CHD type and NYHA FC on QoL and HADS Mean SF-36, CAMPHOR and HADS scores indicated more impairment in female than in male patients for most dimensions.

Mean SF-36, CAMPHOR and HADS scores were independent of the type of PAH-CHD even after gender adjustment (except for CAMPHOR functioning, Table 2).

Mean SF-36, CAMPHOR and HADS scores signi!cantly depended on NYHA FC (Figure 2).

Figure 1. SF-36 scores (n = 208): higher scores indicate better quality of life, p < 0.0001, except for bodily pain, p = 0.005

Table 2. SF-36, CAMPHOR and HADS scores for patients with different types of PAH-CHDEisenmenger

(n = 147)Systemic-to-

pulmonary shunts (n = 25)

Small defects (n = 7)

Corrective cardiac surgery (n = 29)

All PAH-CHD (n = 208)

p-value with/without

gender adjustment

SF-36PCS ± SD 40.5 ± 9.3 41.6 ± 10.4 38.8 ± 8.4 42.3 ± 11.1 40.8 ± 9.6 nsMCS ± SD 44.5 ± 11.1 44.3 ± 9.2 39.3 ± 9.4 46.4 ± 11.2 44.6 ± 10.8 ns

CAMPHORSymptom ± SD 8.8 ± 5.5 9.2 ± 5.9 11.7 ± 3.3 7.7 ± 5.8 8.8 ± 5.6† nsFunctioning ± SD 9.1 ± 5.0 8.0 ± 5.6 6.9 ± 4.1 6.5 ± 4.3 8.5 ± 5.0‡ 0.03/0.04QoL ± SD 6.9 ± 4.6 6.6 ± 4.6 7.1 ± 3.3 5.7 ± 5.7 6.7 ± 5.6‡ ns

HADSAnxiety ± SD 7.1 ± 3.9 7.9 ± 4.0 7.4 ± 2.4 6.8 ± 4.2 7.2 ± 3.9* nsDepression ± SD 4.1 ± 3.9 4.5 ± 2.7 3.1 ± 1.7 3.4 ± 3.7 4.0 ± 3.7† ns

*n = 204, †n = 206, ‡n = 207, p-values (ANOVA) are provided for comparison of subgroups. CAMPHOR, Cambridge Pulmonary Hypertension Outcome Review; CHD, congenital heart disease; HADS, Hospital Anxiety and Depression Scale; ns, non-signi!cant; PAH, pulmonary arterial hypertension; QoL, quality of life; SF-36,

Medical Outcome Study 36-item Short Form Health Survey; PCS/MCS, Physical/Mental component summary.

Multivariate analysis A recent stressful event affected the SF-36 MCS. NYHA FC III/IV was related to all SF-36 and CAMPHOR components with the exception of the SF-36 mental component score (MCS).

6MWD was associated with the SF-36 PCS, and the CAMPHOR symptoms and functioning. HADS anxiety and depression impacted all components of HRQoL except for the SF-36 physical component score (PCS).

Figure 2. (A) SF-36 (B) CAMPHOR and (C) HADS scores for patients in NYHA functional classes I to IV (n = 208). Higher scores indicate better quality of life for SF-36, worse for CAMPHOR and HADS. All scores were signi!cantly different between NYHA functional classes

CONCLUSION

The ACHILLE study is a prospective, cross-sectional, multicentre, observational study that investigated the HRQoL of a large cohort of 208 patients with PAH-CHD in France.

Although patients presented with a stable disease, they had an impaired HRQoL as assessed with both a generic and a PH-speci!c questionnaire.

Higher NYHA FC and HADS scores were associated with worse HRQoL. PAH-CHD patients were prone to anxiety and depression that should be screened for, as support/treatment may be bene!cial.

HRQoL should be more systematically assessed in routine clinical practice, as it is an important consideration in the treatment of PAH-CHD, a disease with a poor prognosis.

REFERENCES1. Duffels MG, et al. Int J Cardiol 2007;120:198–204; 2. Dimopoulos K, et al. Circulation 2010;121:20–25; 3. Becker-Grünig T, et al. Int J Cardiol 2013;168:375–381; 4. Simonneau G, et al. J Am Coll Cardiol 2009;54(1 Suppl):S43–S54.

PCS

US normalised data

SF-3

6 sc

ores

0

10

20

30

40

50

60

MCS Physicalfunctioning

Rolephysical

Bodilypain

Generalhealth

Vitality Socialfunctioning

Roleemotional

Mentalhealth

PCS

SF-3

6 sc

ores

CAM

PHOR

sco

res

0

02468

101214161820

10

20

30

40

50

70

MCS Physicalfunctioning

Rolephysical

Bodilypain

Generalhealth

Vitality Socialfunctioning

Roleemotional

NYHA INYHA III

NYHA IINYHA IV

Mentalhealth

60

Symptoms Functioning Quality of life Anxiety Depression

HADS

sco

res

02468

101214

A

B C

1945

09/09/14 23:30ERS - Programme

Page 1 sur 1https://www.ersnetsecure.org/public/prg_congres.abstract?ww_i_presentation=68287

Monday , 08 September 2014

Hall B2-20 Session 258 12:50-14:40

TP Thematic Poster Session : Pulmonary hypertension: clinical management

P2384Quality of life of patients with pulmonary arterial hypertension associatedwith congenital heart disease: The multicenter cross-sectional ACHILLEstudyP. Amedro, A. Basquin, V. Gressin, P. Clerson, X. Jais, J. B. Thambo, D. Bonnet (Montpellier, Rennes,Paris, Roubaix, Le Kremlin Bicêtre, Bordeaux, France)

Objectives: To assess health-related quality of life (QoL) in patients with pulmonary arterialhypertension associated with congenital heart disease (PAH-CHD) and correlations withclinical status.Methods: This cross-sectional study included PAH-CHD patients in 14 centers in France.QoL was self-reported with a generic questionnaire (SF-36) and a PH-specific questionnaire(CAMPHOR). Patients filled out the Hospital Anxiety and Depression Scale (HADS)questionnaire. Main clinical data were collected.Results: 200 patients were included (mean age 43±SD15.7 years, range 15 to 86 years, 70%female), and were classified as Eisenmenger syndromes (73.5%), PAH associated withsystemic to pulmonary shunts (13%), PAH associated with small defects (3.5%) and PAHafter corrective cardiac surgery (10%). At inclusion, 76.5% patients were receiving PAH-specific treatments. All component scores of both QoL questionnaires showed degradationvs healthy population standard scores. QoL scores were lower in females than in males forall dimensions of both questionnaires (p<0.05). QoL scores were independent of the type ofPAH-CHD but significantly depended on NYHA class even after gender adjustment. In amultivariate analysis, variables significantly affecting QoL included NYHA class, six-minute walk distance, HADS, gender, recent stressful event, and more than onehospitalization within the past 12 months.Conclusion: This study showed degradation of QoL in a large cohort of PAH-CHD patientswith both generic and specific questionnaires. QoL was correlated with NYHA class but notwith the type of PAH-CHD.

INTRODUCTION AND OBJECTIVES

Pulmonary arterial hypertension (PAH) is a severe and frequent (5–10%) complication of congenital heart disease (CHD).1

Nowadays, patients developing PAH associated with CHD (PAH-CHD) are managed in tertiary care PAH-CHD centres, where the introduction of advanced speci!c therapies is expected to improve survival.2

Health-related quality of life (HRQoL) has become an important endpoint in PAH clinical studies, but limited QoL data are available for PAH-CHD patients.3

The objective of the ACHILLE (Adults adolescents Congenital Heart dIsease with puLmonary arteriaL hypertension quality of lifE assessment) study was to assess HRQoL in a large population of patients with PAH-CHD using a generic (SF-36) and a pulmonary hypertension (PH)-speci!c (CAMPHOR) instrument. Factors impacting HRQoL were investigated.

METHODS

Study design Prospective, cross-sectional, observational study Patients enrolled from May 2012 to June 2013 in 14 tertiary care PAH-CHD centres in France

Patients Fifteen years of age or older PAH con!rmed by right heart catheterisation and/or echocardiography PAH-CHD classi!ed according to the Dana Point clinical classi!cation4 as:

– Eisenmenger syndrome – PAH associated with systemic-to-pulmonary shunts – PAH associated with small defects – PAH after corrective cardiac surgery Exclusion criteria:

– Heart transplantation, cardiac surgery without subsequent control, planned corrective heart surgery, recent surgical or intervention catheter procedures (<6 months)

– Patients unable to !ll out the questionnaire

Data collection at inclusion Demographic and clinical data Health-related quality of life questionnaires

– Short form-36 (SF-36v2 Acute, France). 8 domains are assessed These domains are combined to form two higher-order summaries. Each domain and each summary is reported on a scale from 0 to 100. SF-36 scores are normalised to a mean of 50 and standard deviation of 10 based on the normal US population. A higher score indicates better quality of life.

– Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). The CAMPHOR is divided into three separate scales. Scores range 0–25 for the symptom and QoL scales and 0–30 for the functioning scale. A higher score indicates worse QoL.

Anxiety and depression. – Hospital Anxiety and Depression Scale (HADS). A score between 0 and 3 is assigned to

each item. The total scores for depression and for anxiety range between 0 and 21. We considered a HADS anxiety or depression score "8 represented symptoms of anxiety or depression.

Amedro P1, Basquin A2, Gressin V3, Clerson P4, Jaïs X5, Thambo JB6, Bonnet D7

1Hôpital Arnaud de Villeneuve, Montpellier, France; 2CHU Rennes, France; 3Actelion Pharmaceuticals France, Paris, France; 4Interphase Orgamétrie Biostatistics, Roubaix, France; 5Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; 6Hôpital cardiologique du Haut-Lévêque, Bordeaux, France; 7M3C-Necker, Paris, France

Quality of life of patients with pulmonary arterial hypertension associated with congenital heart disease: The multicentre cross-sectional ACHILLE study

Disclosures: This study was sponsored by Actelion Pharmaceuticals France. PA, XJ, JBT and DB received reimbursements, fees, and/or funding from Actelion Pharmaceuticals France. PC provided statistical analysis, funded by Actelion Pharmaceuticals France. VG is a full time employee of Actelion Pharmaceuticals France. DB exerts consultant activities for P!zer, Bayer, Eli Lilly, and GSK. AB reports no con"ict of interest. Acknowledgements: The authors are thankful to the ACHILLE study investigators from M3C-Georges Pompidou European Hospital, Paris (S Cohen, L Iserin, M Ladouceur, O Sanchez, A Legendre); Bicêtre University Hospital, Le Kremlin-Bicêtre (X Jaïs, O Sitbon); Guillaume and René Laennec Hospital, Nantes (P Guérin, L Le Gloan); Louis Pradel Hospital -cardiology/ respiratory diseases- Bron (A Sénéchal, V Cottin, A Sou!, J Traclet, C Khouatra); Côte de Nacre Hospital, Caen (F Lalombarda, E Bergot, P Maragnes); Charles Nicolle Hospital, Rouen (E Barre); University Hospital, Rennes (J-M Schleich); Gabriel-Montpied University Hospital Clermont-Ferrand (C Dauphin, J-R Lusson); M3C-Necker University Hospital, Paris (M Levy); Haut-Lévêque University Hospital, Bordeaux (X Iriart, M de Guillebon); Albert Michallon Hospital, La Tronche (H Bouvaist); Marie Lannelongue Chirurgical centre, Le Plessis Robinson (A Baruteau, V Lambert, M Gouton), France. Medical writing support was provided by Sylvie Ertel PhD (Sundgau Medical Writers, Habsheim, France) and was funded by Actelion Pharmaceuticals Ltd. Poster presented at the European Respiratory Society, 6–10 September 2014, Munich, Germany.

Statistical analysis Characteristics of patients were compared according to the type of CHD or to New York Heart Association (NYHA) functional class (FC) by analysis of variance (ANOVA) for continuous variables and chi-squared or exact Fisher’s test for categorical variables.

Univariate and multivariate regression analyses were performed to identify the covariates impacting the QoL among the following: gender, age per quartile, time since diagnosis of CHD and of PAH, HADS, 6-minute walk distance (6MWD), NYHA FC, at least one hospitalisation due to PAH and/or CHD in the past 12 months, and recent stressful event.

A signi!cance level of p # 0.05 was used.

RESULTS

Population 208 patients were included in the analysis (Table 1).

Table 1. Characteristics at inclusionPatients with PAH-CHD (n = 208)

DemographicsAge, years ± SD (range) 42.6 ± 15.8 (15.1–85.8)Female gender, n (%) 145 (69.7)

Clinical characteristicsAge at PAH diagnosis, years ± SD (range) 25.9 ± 20.3 [0–80.0]Classi!cation of CHD associated with PAH

Eisenmenger syndrome 147 (70.7)PAH with systemic-pulmonary shunt 25 (12.0)PAH with small defects 7 (3.4)PAH after corrective cardiac surgery 29 (13.9)

At least one hospitalisation in the past 12 months*, n (%) 142 (68.3)NYHA FC I: II: III: IV, % 10.6: 48.1: 37.5: 3.96-minute walk distance, m ± SD 431 ± 109 (n = 147)Clinical status stable for the past 3 months, n (%) 184 (86.0)

PAH-speci!c treatments†, n (%)No treatment 49 (23.6)Monotherapy 85 (40.9)Double combination therapy 66 (31.7)Triple combination therapy 8 (3.9)

Values are expressed as mean ± standard deviation unless otherwise speci!ed; *Hospitalisation due to PAH and/or CHD; †Endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, and/or prostanoid. CHD, congenital heart disease; NYHA FC, New York Heart Association functional class; PAH, pulmonary arterial hypertension.

Health-related quality of life Mean SF-36 scores were low compared with the US normalised mean of 50 for all domains (Figure 1) indicating decreased QoL.

Mean CAMPHOR symptom, functioning, and QoL scores among PAH-CHD patients were 8.8 ± 5.6, 8.5 ± 5.0 and 6.7 ± 5.6, respectively.

Hospital anxiety and depression (HADS) Anxiety and depression component scores of the HADS questionnaire were 7.2 ± 3.9 and 4.0 ± 3.7, respectively.

HADS anxiety and depression scores were above 8 (representing symptoms of anxiety or depression) for 64 patients (31.4%) and 19 patients (9.2%), respectively.

Effect of gender, PAH-CHD type and NYHA FC on QoL and HADS Mean SF-36, CAMPHOR and HADS scores indicated more impairment in female than in male patients for most dimensions.

Mean SF-36, CAMPHOR and HADS scores were independent of the type of PAH-CHD even after gender adjustment (except for CAMPHOR functioning, Table 2).

Mean SF-36, CAMPHOR and HADS scores signi!cantly depended on NYHA FC (Figure 2).

Figure 1. SF-36 scores (n = 208): higher scores indicate better quality of life, p < 0.0001, except for bodily pain, p = 0.005

Table 2. SF-36, CAMPHOR and HADS scores for patients with different types of PAH-CHDEisenmenger

(n = 147)Systemic-to-

pulmonary shunts (n = 25)

Small defects (n = 7)

Corrective cardiac surgery (n = 29)

All PAH-CHD (n = 208)

p-value with/without

gender adjustment

SF-36PCS ± SD 40.5 ± 9.3 41.6 ± 10.4 38.8 ± 8.4 42.3 ± 11.1 40.8 ± 9.6 nsMCS ± SD 44.5 ± 11.1 44.3 ± 9.2 39.3 ± 9.4 46.4 ± 11.2 44.6 ± 10.8 ns

CAMPHORSymptom ± SD 8.8 ± 5.5 9.2 ± 5.9 11.7 ± 3.3 7.7 ± 5.8 8.8 ± 5.6† nsFunctioning ± SD 9.1 ± 5.0 8.0 ± 5.6 6.9 ± 4.1 6.5 ± 4.3 8.5 ± 5.0‡ 0.03/0.04QoL ± SD 6.9 ± 4.6 6.6 ± 4.6 7.1 ± 3.3 5.7 ± 5.7 6.7 ± 5.6‡ ns

HADSAnxiety ± SD 7.1 ± 3.9 7.9 ± 4.0 7.4 ± 2.4 6.8 ± 4.2 7.2 ± 3.9* nsDepression ± SD 4.1 ± 3.9 4.5 ± 2.7 3.1 ± 1.7 3.4 ± 3.7 4.0 ± 3.7† ns

*n = 204, †n = 206, ‡n = 207, p-values (ANOVA) are provided for comparison of subgroups. CAMPHOR, Cambridge Pulmonary Hypertension Outcome Review; CHD, congenital heart disease; HADS, Hospital Anxiety and Depression Scale; ns, non-signi!cant; PAH, pulmonary arterial hypertension; QoL, quality of life; SF-36,

Medical Outcome Study 36-item Short Form Health Survey; PCS/MCS, Physical/Mental component summary.

Multivariate analysis A recent stressful event affected the SF-36 MCS. NYHA FC III/IV was related to all SF-36 and CAMPHOR components with the exception of the SF-36 mental component score (MCS).

6MWD was associated with the SF-36 PCS, and the CAMPHOR symptoms and functioning. HADS anxiety and depression impacted all components of HRQoL except for the SF-36 physical component score (PCS).

Figure 2. (A) SF-36 (B) CAMPHOR and (C) HADS scores for patients in NYHA functional classes I to IV (n = 208). Higher scores indicate better quality of life for SF-36, worse for CAMPHOR and HADS. All scores were signi!cantly different between NYHA functional classes

CONCLUSION

The ACHILLE study is a prospective, cross-sectional, multicentre, observational study that investigated the HRQoL of a large cohort of 208 patients with PAH-CHD in France.

Although patients presented with a stable disease, they had an impaired HRQoL as assessed with both a generic and a PH-speci!c questionnaire.

Higher NYHA FC and HADS scores were associated with worse HRQoL. PAH-CHD patients were prone to anxiety and depression that should be screened for, as support/treatment may be bene!cial.

HRQoL should be more systematically assessed in routine clinical practice, as it is an important consideration in the treatment of PAH-CHD, a disease with a poor prognosis.

REFERENCES1. Duffels MG, et al. Int J Cardiol 2007;120:198–204; 2. Dimopoulos K, et al. Circulation 2010;121:20–25; 3. Becker-Grünig T, et al. Int J Cardiol 2013;168:375–381; 4. Simonneau G, et al. J Am Coll Cardiol 2009;54(1 Suppl):S43–S54.

PCS

US normalised data

SF-3

6 sc

ores

0

10

20

30

40

50

60

MCS Physicalfunctioning

Rolephysical

Bodilypain

Generalhealth

Vitality Socialfunctioning

Roleemotional

Mentalhealth

PCS

SF-3

6 sc

ores

CAM

PHOR

sco

res

0

02468

101214161820

10

20

30

40

50

70

MCS Physicalfunctioning

Rolephysical

Bodilypain

Generalhealth

Vitality Socialfunctioning

Roleemotional

NYHA INYHA III

NYHA IINYHA IV

Mentalhealth

60

Symptoms Functioning Quality of life Anxiety Depression

HADS

sco

res

02468

101214

A

B C

1945

La dimension physique de la QdV est corrélée à la sévérité de l’HTAP-CC (Amedro et al. ERS 2014)

17

QdV des ACHD parfois meilleure que celle de la population générale :

forme de résilience?

• Moons et al. Eur J Cardiovasc Nurs. 2013

• «disability paradox» : handicap sévère associé à une bonne QdV

• «response shift» : le patient s’adapte à son déficit en modifiant ses priorités

• «sense of coherence» : les ACHD peuvent avoir un haut niveau d’acceptation et de compréhension de leur maladie

• L’utilisation de questionnaires spécifiques et génériques chez ces malades peuvent montrer ce phénomène

18

Exemple de questionnaire spécifique de l’hypertension pulmonaire : le Camphor

Veuillez lire attentivement

Dan les pages suivantes vous trouverez des commentaries fait par des

personnes atteintes de l’hypertension artérielle pulmonaire.

Cochez la case ‘Vrai’ si l’énoncé s’applique à votre situation

et ‘Faux’ dans le cas contraire

N’oubliez pas de cocher qu’une seule case par énoncé

Veuillez choisir la réponse qui s’applique le mieux à

votre situation actuelle

© Galen Research & Papworth Hospital, 2004

CAMPHOR

Cambridge Pulmonary Hypertension Outcome Review

3 échelles :

- symptômes liés à l’HTAP : 25 items, oui (1)/non (0) => 0 à 25 points (score élevé = HTAP sévère)

. énergie (10)

. manque d’air (8)

. humeur (6)

- état fonctionnel : capacités physiques => 15 items, scores de 0 (oui sans pb),1 (oui avec difficulté, 2 (impossible), score total de 0 à 30 (score élevé = HTAP sévère)

- QDV : 25 questions => vrai(1)/faux(0), score élavé = mauvaise QdV

19

QdV des patients ACHD les plus sévères

• n=208 HTAP-CC

• questionnaire CAMPHOR

Les dimensions non physiques de la QdV ne sont pas corrélées à la sévérité de l’HTAP-CC

Amedro et al. ERS 2014

20

Adolescents Cardiaques Congénitaux : début du processus de résilience?

KidscreenScore

Controlsn=164

CHD children and teenagers

n=282

PedsQLScore Severity

ScoreVO2max

CHD

Type

Quality of life of children with congenital heart diseases: a multi-center controlled cross-sectional study. Amedro et al. ESC 2014

The European Society of Cardiology (ESC) is an

association representing over 80 000 cardiology

professionals internationally.

The ESC provides educational courses and

certification, produces highly respected clinical

practice guidelines, and publishes leading

journals, textbooks and other scientific materials.

It also oversees important surveys and registries,

as well as being actively involved in advocacy

initiatives.

ESC Congress, the society’s annual congress,

is the largest cardiology meeting in the world.

The ESC also organises several well established

sub-specialty cardiology congresses.

Membership is possible through one of the

ESC’s National Cardiac Societies, sub-specialty

Associations, Working Groups or Councils, as

well as through the distinguished community of

Fellows of the ESC.

Joining the ESC will strengthen your position

in the field of cardiology and open up a world

of possibilities for sharing knowledge and

experience, networking and advancing your

career.

Come and visit us at the ESC Stand for more information

www.escardio.org

Be part of it!

21

Adolescents Cardiaques Congénitaux : début du processus de résilience?

Quality of life of children with congenital heart diseases: a multi-center controlled cross-sectional study. Amedro et al. ESC 2014

The European Society of Cardiology (ESC) is an

association representing over 80 000 cardiology

professionals internationally.

The ESC provides educational courses and

certification, produces highly respected clinical

practice guidelines, and publishes leading

journals, textbooks and other scientific materials.

It also oversees important surveys and registries,

as well as being actively involved in advocacy

initiatives.

ESC Congress, the society’s annual congress,

is the largest cardiology meeting in the world.

The ESC also organises several well established

sub-specialty cardiology congresses.

Membership is possible through one of the

ESC’s National Cardiac Societies, sub-specialty

Associations, Working Groups or Councils, as

well as through the distinguished community of

Fellows of the ESC.

Joining the ESC will strengthen your position

in the field of cardiology and open up a world

of possibilities for sharing knowledge and

experience, networking and advancing your

career.

Come and visit us at the ESC Stand for more information

www.escardio.org

Be part of it!

• Dans les 2 groupes témoins et CC

• scores QdV filles < garçons

• scores QdV parents < enfants

• scores adolescents (13-18 ans) < enfants (8-12 ans)

• Mais si on compare CC vs témoins

• scores physiques CC < témoins chez les jeunes

• scores QdV adolescents identiques +++

22

Conclusion• L’évaluation de la qualité de vie devrait faire

partie de la routine dans le suivi des patients avec CC

• La dimension physique de la QdV est corrélée à la sévérité de la CC et les scores peuvent être utilisés comme «PRO»

• Les autres dimensions sont plus subtiles à interpréter, avec un processus proche de la résilience

• Attention aux biais : dépression, anxiété

• Les perspectives en recherche clinique comme critère de jugement principal ou secondaire sont considérables :

• binôme VO2-QDV prometteur

• évolution de la QdV dans le temps23