Céline Chabanne

Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension

Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis. Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min−1·m−2. 1017 patients were included (mean age 57 years, 59% female, 75% idiopathic PAH). After a median follow-up of 34 months, 238 (23%) patients had died. Each of the four low-risk criteria independently predicted transplant-free survival at first re-evaluation. The number of low-risk criteria present at diagnosis (p<0.001) and at first re-evaluation (p<0.001) discriminated the risk of death or lung transplantation. In addition, in a subgroup of 603 patients with brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements, the number of three noninvasive criteria (WHO/NYHA functional class, 6MWD and BNP/NT-proBNP) present at first re-evaluation discriminated prognostic groups (p<0.001). A simplified risk assessment tool that quantifies the number of low-risk criteria present accurately predicted transplant-free survival in PAH. Simplified risk assessment using the number of low-risk criteria predicts prognosis at baseline and follow-up in PAH http://ow.ly/KMsj30cPNbm

Argument for a Doppler echocardiography during exercise in assessing asymptomatic patients with severe aortic stenosis.

AIMS Exercise stress testing (EST) is recommended by guidelines to risk-stratify patients with asymptomatic valvular aortic stenosis (AS), though the role of quantitative exercise-Doppler echocardiography has rarely been studied. This prospective study sought to correlate standard EST results with the haemodynamic measurements made during exercise by Doppler echocardiography. METHODS AND RESULTS We performed rest and semi-supine exercise Doppler echocardiography in 44 consecutive patients (mean age=68+/-12 years) with aortic valve areas<or=0.6 cm2/m2. The effective aortic valve area (EOA), cardiac output (CO), maximal transvalvular velocity, and pulmonary pressure were monitored over the test. No serious adverse event was observed. EST was positive in 26 (Group 1) and negative in 18 (Group 2) patients. Baseline echocardiographic measurements were similar (EOA 0.77+/-0.15 vs. 0.78+/-0.14 cm2; CO 5.5+/-1.6 vs. 5.9+/-2 L/min) in both groups. Exercise-induced changes in CO (+2.9+/-2 vs. +4.3+/-1.8 L/min, P=0.04) and EOA (-0.04+/-0.18 vs. +0.15+/-0.24 cm2, P=0.015) were significantly greater in Group 2. A correlation between changes in EOA and changes in CO during exercise was observed, but significantly higher in Group 2 (P=0.04). CONCLUSION In the presence of severe asymptomatic AS, exercise Doppler echocardiography, assessing the mechanisms behind a positive EST, appears very promising but further studies with prognosis assessment remain necessary.

A prospective study of the 6 min walk test as a surrogate marker for haemodynamics in two independent cohorts of treatment-naïve systemic sclerosis-associated pulmonary arterial hypertension.

Objectives Despite the wide use of the 6 min walk distance (6MWD), no study has ever assessed its validity as a surrogate marker for haemodynamics and predictor of outcome in isolated pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH). We designed this work to address this issue. Methods Treatment-naïve patients with SSc-PAH were prospectively included from two sources: the French PAH Network (a prospective epidemiological cohort) (n=83) and randomised clinical trials submitted for drug approval (Food and Drug Administration) (n=332). Correlations between absolute values of the 6MWD and haemodynamics at baseline, as well as between variations of 6MWD and haemodynamics during follow-up, were studied in both populations. Results In the French cohort, baseline cardiac output (CO) (R2=0.19, p=0.001) and New York Heart Association class (R2=0.10, p<0.001) were significantly and independently correlated with baseline 6MWD in multivariate analysis. A significant, independent, but weaker, correlation with CO was also found in the Food and Drug Administration sample (R2=0.04, p<0.001). During follow-up, there was no association between the changes in 6MWD and haemodynamic parameters in patients under PAH-specific treatments. Conclusions In SSc-PAH, CO independently correlates with 6MWD at baseline, but accounts for a small amount of the variance of 6MWD in both study samples. This suggests that other non-haemodynamic factors could have an impact on the walk distance. Moreover, variations of 6MWD do not reflect changes in haemodynamics among treated patients. Our results suggest that 6MWD is not an accurate surrogate marker for haemodynamic severity, nor an appropriate outcome measure to assess changes in haemodynamics during follow-up in treated SSc-PAH.

Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry

Background Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE). Methods We identified all patients with SLE and PAH (SLE‐PAH) who were enrolled in the French Pulmonary Hypertension Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 patients with SLE without known PAH was selected from SLE expert centers participating in the Pulmonary Hypertension Registry. Survival was estimated by the Kaplan‐Meier method. Hazard ratios associated with potential predictors of death were estimated using Cox proportional hazard models. Results Of the 69 patients with SLE‐PAH identified in the French Pulmonary Hypertension Registry, 51 were included in the study. They did not differ from the control group regarding age, sex, or duration of SLE at the time of the analysis but had a higher frequency of anti‐SSA and anti‐SSB antibodies. The delay between SLE diagnosis and PAH diagnosis was 4.9 years (range, 2.8‐12.9) years. The 3‐ and 5‐year overall survival rates were 89.4% (95% CI, 76.2%‐96.5%) and 83.9% (95% CI, 68.8%‐92.1%), respectively. The survival rate was significantly better in patients with anti‐U1‐RNP antibodies (P = .04). Conclusions Patients with SLE‐PAH have an overall 5‐year survival rate of 83.9% after the PAH diagnosis. Anti‐SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti‐U1‐RNP antibodies appears to be a protective factor regarding survival.

Comparison of cardiac allograft vasculopathy in heart and heart–lung transplantations: A 15-year retrospective study

BACKGROUND Cardiac allograft vasculopathy (CAV) is a major factor limiting long-term survival after heart transplantation (HTx). Specific determinants of CAV and long-term outcome after CAV occurrence have been poorly investigated after heart-lung transplantation (HLTx). METHODS Between January 1996 and December 2006, 79 patients underwent HLTx (36.3 ± 12.2 years old; 47% men) and 141 patients underwent HTx (49.2 ± 12.3 years old; 77% men) at two different institutions. CAV grading was reviewed in both groups according to the 2010 standardized nomenclature of the International Society for Heart and Lung Transplantation. The mean post-transplant follow-up was 94 (1 to 181) months. RESULTS Overall 10-year survival rate was 58% after HTx and 43% after HLTx (p = 0.11). The Grade 1 (or higher) CAV-free survival rate was 95% at 4 years and 69% at 10 years after HLTx, and 77% and 39%, respectively, after HTx (p < 0.01). Mean cyclosporine blood levels were similar between the groups at 3, 6, 12, 24 and 36 months. The main causes of mortality beyond 5 years after HTx and HLTx were malignancies and bronchiolitis obliterans, respectively. By multivariate analysis, recipients who developed >3 acute myocardial rejections during the first year post-transplant were exposed to a higher risk of CAV (95% CI 1.065 to 2.33, p = 0.02). Episodes of acute pulmonary rejection and bronchiolitis obliterans were not associated with an increased risk of CAV (p = 0.52 and p = 0.30). CONCLUSION HLTx recipients appeared protected from CAV compared with HTx patients in this retrospective study. Repeated acute cardiac rejections were independent predictors of CAV. Unlike bronchiolitis obliterans, CAV had a very low impact on long-term survival after HLTx.

Three-year haemodynamic performance of the St Jude Trifecta bioprosthesis.

OBJECTIVES To examine the haemodynamic performance of the St Jude Trifecta valve for aortic valve replacement (AVR) at 3 years after implantation. METHODS In a single-centre, prospective, observational, independent study, we enrolled 122 patients who had AVR using a Trifecta bioprosthesis in the July 2010-June 2011 period. A clinical and echocardiographic in-house follow-up was scheduled. RESULTS In our series, 14.7% of patients received a 19-mm, 28.7% had a 21-mm, 35.2% had a 23-mm and 21.3% had a greater-size prosthesis. There were no cases of operative mortality or of valve-related complications both early and at follow-up (except one sudden unexplained death). Completeness of the 3-year echocardiographic follow-up was 80% among survivors. The average mean transvalvular gradient (mTVG) at 3 years was 14.2, 10.8, 8.6, 7.1 and 6.8 mmHg (sizes 19 to 27/29, respectively). There was no statistically significant difference between average mTVGs measured immediately after implantation versus at the 3-year follow-up in the overall population. The average peak transvalvular gradient (pTVG) at 3 years was 25, 20, 16.8, 13.9 and 14.4 mmHg (sizes 19 to 27/29, respectively). The average indexed effective orifice area (iEOA) at 3 years was 0.8, 0.9, 1, 1.3 and 1.3 cm(2)/m(2) (sizes 19-27, respectively). The rate of moderate patient-prosthesis mismatch (PPM) at 3 years was 15.7%; there were two instances of severe PPM (2.2%). All cases of PPM occurred in the 19, 21 and 23 mm size subgroups. CONCLUSIONS The Trifecta valve retains its excellent haemodynamic properties at the 3-year follow-up. The rate of PPM is considerably low.

Heart transplantation as salvage treatment of intractable infective endocarditis.

This study reports six consecutive patients who underwent heart transplantation as salvage treatment for endocarditis (Duke criteria) with extensive perivalvular lesions and end-stage heart failure. The median age was 45 years (range, 24 to 64), and the aortic valve was affected in all patients. Pathogens were Staphylococcus aureus (n = 2), Streptococcus pneumoniae (n = 2), Streptococcus agalactiae (n = 1), or not documented (n = 1). All patients survived, with no relapse, after a median follow-up of 24.5 months. The 10 patients with heart transplantation for endocarditis previously reported also survived (median follow-up, 27.5 months). Heart transplantation may be considered as salvage treatment in selected patients with intractable infective endocarditis.

Heterotopic heart transplantation: where do we stand?

Orthotopic heart transplantation (OHT) is a well established and commonly utilized procedure for end-stage heart failure patients. Heterotopic heart transplantation (HHT) is a surgical procedure that allows the graft to be connected to the native heart in a parallel fashion. The main advantage of HHT is to assist the patients native heart and to maintain circulation in the cases of severe acute rejection. HHT has also been proposed to overcome pulmonary hypertension, to increase the size of the donor pool and to decrease waiting times without increasing morbidity caused by the procedure. However, only a few papers have reported the short- or long-term results of HHT, and most of these studies have included <30 cases. OHT remains the standard technique and is preferable whenever the patient meets the current criteria and a suitable organ is available. HHT is far less useful than in the past because of the major advances in immunosuppression therapy and the development of long-term mechanical circulatory support. This study reviews the origin of HHT and discusses clinical developments, including their advantages and disadvantages.

Impact of donor comorbidities on heart transplant outcomes in the modern era

OBJECTIVES The use of marginal donors with cardiovascular risk factors is increasing due to organ shortage but remains controversial in heart transplantation (HTx). We sought to investigate post-transplant outcomes in the recent era taking into account donor characteristics. METHODS We reviewed 261 HTx performed in our hospital between January 1996 and March 2013. Donor characteristics were obtained from the national database. The incidence of primary graft dysfunction (PGD) and cardiac allograft vasculopathy (CAV) and overall survival were compared in 2 groups of HTx recipients: those receiving transplants from 1996 to 2004 (Group A, n =  120) and from 2005 to 2013 (Group B, n =  141). RESULTS The mean age of the donors was 34 ± 12 years in Group A vs 42 ± 13 years in Group B ( P  < 0.001). Donors in Group B had a higher body mass index (23 ± 2 vs 26 ± 5 kg/m 2 , P  < 0.001), were more likely to be smokers (29.6% vs 52.9%, P  < 0.001) and were more likely to have hypertension (5% vs 13.5%, P  = 0.030). There was no difference in survival at 1 and 5 years (79% and 63% in Group A vs 80% and 62% in Group B, respectively; P  = 0.551). The rate of PGD was 36% in Group A vs 40% in Group B ( P  = 0.092). Freedom from CAV at 5 years was 64% and 61%, respectively ( P  = 0.367). Among the characteristics of the donors, only hypertension was associated with reduced survival. CONCLUSIONS The use of older cardiac donors with more cardiovascular comorbidities in the recent era did not impair the post-transplant outcomes. Donor hypertension was the only determinant of worse survival.

Oral pulmonary vasoactive drugs achieve hemodynamic eligibility for liver transplantation in portopulmonary hypertension

BACKGROUND AND AIMS Portopulmonary hypertension (POPH) hampers survival of patients with cirrhosis and portal hypertension and may preclude liver transplantation (LT). Management of such patients with oral pulmonary vasoactive drugs (PVD) has not been standardized. Our aim was to assess the efficacy and safety of oral PVD for management of POPH. METHODS All patients treated by oral PVD (bosentan, ambrisentan, sildenafil, tadalafil) for POPH were retrospectively studied. Significant response was defined for the patients who reached the following LT eligibility criteria: mean pulmonary artery pressure (MPAP) <35mmHg or MPAP between 35 and 50mmHg with pulmonary vascular resistance (PVR) <250dynscm-5. RESULTS 20 patients were followed for 38 (19-57) months. Oral PVD improved MPAP (-8 [-19, +2]mmHg), PVR (-201 [-344, -68]dynscm-5) and 6-min walk distance (+52 [-51, +112] m). Fifty-three percent of evaluable patients reached eligibility to LT criteria, of whom 5 were transplanted. Baseline MPAP>51mmHg and/or PVR>536dynscm-5 predicted non response to treatment. Five-years survival was 53%. No worsening of cirrhosis or serious adverse effect was recorded. CONCLUSION Oral pulmonary vasoactive drugs are safe in cirrhotic patients with POPH. These treatments improved hemodynamic conditions allowing patients access to liver transplantation eligibility.