Heart Transplantation for Peripartum Cardiomyopathy: A Single-Center Experience

Abstract Background: Peripartum cardiomyopathy is an idiopathic disorder defined by the occurrence of acute heart failure during late pregnancy or post-partum period in the absence of any other definable cause. Its clinical course is variable and severe cases might require heart transplantation. Objective: To investigate long-term outcomes after heart transplantation (HT) for peripartum cardiomyopathy (PPCM). Methods: Out of a single-center series of 1938 HT, 14 HT were performed for PPCM. We evaluated clinical characteristics, transplant-related complications, and long-term outcomes, in comparison with 28 sex-matched controls. Primary endpoint was death from any cause; secondary endpoints were transplant-related complications (rejection, infection, cardiac allograft vasculopathy). A value of p 0.05), except for a higher use of inotropes at the time of HT in PPCM group (p = 0.03). During a median follow-up of 7.7 years, 16 patients died, 3 (21.5%) in PPCM group and 13 (46.5%) in control group. Mortality was significantly lower in PPCM group (p = 0.03). No significant difference was found in terms of transplant-related complications (p > 0.05). Conclusions: Long-term outcomes following HT for PPCM are favorable. Heart transplantation is a valuable option for PPCM patients who did not recover significantly under medical treatment

A single-center long-term experience with marginal donor utilization for heart transplantation

Background To evaluate the early and late outcome of heart transplantation (HT) using marginal (MDs) and optimal donors (ODs). Methods Clinical records of recipients transplanted between July 2004 and December 2014 were retrospectively reviewed. MDs were defined as follows: age >55 years, high-dose inotropic support, left ventricular ejection fraction <45%, left ventricular hypertrophy, donor to recipient predicted heart mass ratio <0.86, ischemic time >4 hours. Results A total of 412 (55%) recipients received an organ from a MD; recipients who received an organ from an OD had less primary graft dysfunction (PGD) (25% vs 38%;P < .001), less acute renal failure (23% vs 34%;P < .001), and higher survival rates (90.2% vs 81.8% at 30 days, 79.5% vs 71.1% at 1 year, 51.8% vs 45.4% at 12 years;P = .01) than recipients who received an organ from a MD. There was no statistically significant difference in 30-day conditional survival between the two groups (survival rates 57.4% vs 55.5% at 12 years;P = .43). PGD, perioperative hemodialysis, and sepsis were independent risk factors of mortality at multivariate analysis. Conclusions Utilization of MDs for HT is associated with a higher incidence of PGD and acute renal failure, and a reduction of 30-day survival

Performance of existing risk scores around heart transplantation: validation study in a 4-year cohort

International audienceSeveral risk scores exist to help identify best candidate recipients for heart transplantation (HTx). This study describes the performance of five heart failure risk scores and two post-HTx mortality risk scores in a French single-centre cohort. All patients listed for HTx through a 4-year period were included. Waiting-list risk scores [Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC), Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) and Get With The Guidelines-Heart Failure (GWTG-HF)] and post-HTx scores Index for Mortality Prediction After Cardiac Transplantation (IMPACT and CARRS) were computed. Main outcomes were 1-year mortality on waiting list and after HTx. Performance was assessed using receiver operator characteristic (ROC), calibration and goodness-of-fit analyses. The cohort included 414 patients. Waiting-list mortality was 14.0%, and post-HTx mortality was 16.3% at 1-year follow-up. Heart failure risk scores had adequate discrimination regarding waiting-list mortality (ROC AUC for HFSS = 0.68, SHFM = 0.74, OPTIMIZE-HF = 0.72, MAGGIC = 0.70 and GWTG = 0.77; all P-values <0.05). On the contrary, post-HTx risk scores did not discriminate post-HTx mortality (AUC for IMPACT = 0.58, and CARRS = 0.48, both P-values >0.50). Subgroup analysis on patients undergoing HTx after ventricular assistance device (VAD) implantation (i.e. bridge-to-transplantation) (n = 36) showed an IMPACT AUC = 0.72 (P < 0.001). In this single-centre cohort, existing heart failure risk scores were adequate to predict waiting-list mortality. Post-HTx mortality risk scores were not, except in the VAD subgroup

N-acetyl cysteine alleviates oxidative stress and protects mice from dilated cardiomyopathy caused by mutations in nuclear A-type lamins gene

International audienceCardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscular and electrical dysfunction of the heart, often leading to heart failure-related disability. There is currently no specific therapy available for patients that target the molecular pathophysiology of LMNA cardiomyopathy. We showed here an increase in oxidative stress levels in the hearts of mice carrying LMNA mutation, associated with a decrease of the key cellular antioxidant glutathione (GHS). Oral administration of N-acetyl cysteine, a GHS precursor, led to a marked improvement of GHS content, a decrease in oxidative stress markers including protein carbonyls and an improvement of left ventricular structure and function in a model of LMNA cardiomyopathy. Collectively, our novel results provide therapeutic insights into LMNA cardiomyopathy

A single‐center long‐term experience with marginal donor utilization for heart transplantation

Background To evaluate the early and late outcome of heart transplantation (HT) using marginal (MDs) and optimal donors (ODs). Methods Clinical records of recipients transplanted between July 2004 and December 2014 were retrospectively reviewed. MDs were defined as follows: age &gt;55 years, high-dose inotropic support, left ventricular ejection fraction &lt;45%, left ventricular hypertrophy, donor to recipient predicted heart mass ratio &lt;0.86, ischemic time &gt;4 hours. Results A total of 412 (55%) recipients received an organ from a MD; recipients who received an organ from an OD had less primary graft dysfunction (PGD) (25% vs 38%;P &lt; .001), less acute renal failure (23% vs 34%;P &lt; .001), and higher survival rates (90.2% vs 81.8% at 30 days, 79.5% vs 71.1% at 1 year, 51.8% vs 45.4% at 12 years;P = .01) than recipients who received an organ from a MD. There was no statistically significant difference in 30-day conditional survival between the two groups (survival rates 57.4% vs 55.5% at 12 years;P = .43). PGD, perioperative hemodialysis, and sepsis were independent risk factors of mortality at multivariate analysis. Conclusions Utilization of MDs for HT is associated with a higher incidence of PGD and acute renal failure, and a reduction of 30-day survival

Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

International audienceBACKGROUND:HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency.METHODS:In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data.RESULTS:Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, p=0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β= 0.44 (0.35;1.27) and -0.44 (-0.94;-0.26) respectively, both p-values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β= 0.25 (0.04;0.41), p=0.001) and estradiol (β= -0.22 (-0.57;-0.02), p<0.001).CONCLUSION:CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G