Female Heart Transplant Recipients Research Articles

Differences in excess mortality by recipient sex after heart transplant: An individual patient data meta-analysis

BackgroundIdentification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female versus male heart transplant recipients. MethodsWe used relative survival models conducted separately in SRTR and CTS cohorts from 1988–2019, and subsequently combined using two-stage individual patient data meta-analysis, to compare the excess risk of mortality in female versus male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age. ResultsWe analyzed 108,918 patients. When the donor was male, female recipients 0–12 years (Relative excess risk (RER) 1.13, 95% CI 1.00–1.26), 13–44 years (RER 1.17, 95% CI 1.10–1.25), and ≥45 years (RER 1.14, 95% CI 1.02–1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13–44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00–1.20), though not significantly (p= 0.05). ConclusionsIn the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences.

Informing preconception counseling: Outcomes among female heart transplant recipients in the ISHLT registry

The numbers of women of child-bearing age undergoing heart transplantation (HT) and female pediatric HT recipients surviving to child-bearing age have increased, along with improvements in post-transplant survival. Data regarding life expectancy and comorbidities in reproductive-aged female HT recipients are needed to inform shared decision-making at the time of preconception counseling. The International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry was investigated for HT recipients between January 1, 2000 and June 30, 2017. Women of childbearing age were defined as those aged 15-45 years, either at transplant, or at the respective post-transplant follow-up. Characteristics and outcomes of female recipients of childbearing age at transplant, 5-, 10-, and 15-year follow-up were compared to females>45 years of age, males 15-45 years and males>45 years of age at the corresponding time intervals. Outcomes included survival, development of diabetes (DM), severe renal dysfunction (CKD), and cardiac allograft vasculopathy (CAV). During the study period, 71,585 HT recipients were included: 24% (n=17,194) were female and 9.2% (n=6602) were of childbearing age at HT. A pre-transplant diagnosis of peripartum cardiomyopathy was associated with significantly worse post-transplant survival, a finding that remained independent of panel reactive antibody levels. The presence of pre-transplant DM and/or severe CKD was significantly associated with lower survival as were the presence of CAV, DM, and CKD post-HT. Knowledge of the impact of pre-existing comorbidities and complications post-HT on survival are important for risk stratification for preconception counseling post-HT.

Attitudes & practices surrounding pregnancy post heart transplant among pediatric providers.

Many pediatric heart transplant (HT) recipients reach adulthood and may be interested in family planning; there is little data regarding safety of pregnancy post HT and clinicians' opinions differ. Pediatric HT clinicians are instrumental in early counseling. Thus, a better understanding of pediatric HT clinicians' practices regarding family planning and how well aligned these practices are with adult transplant centers is essential. We conducted a confidential, web-based survey of pediatric HT clinicians in fall 2021. We summarized and compared answers using Fisher's exact test. The survey was sent to 53 United States-based HT directors and to the International Society for Heart and Lung Transplantation and Pediatric Heart Transplant Society list serves. There were 69 respondents. The majority (77%) of respondents felt pregnancy was feasible in selected or all female HT recipients. Ten respondents reported that their institution had an established policy regarding pregnancy post HT. A majority (77%) of HT clinicians would either use a shared care model or recommend transition to their adult institution if pregnancy occurred, though 74% of respondents were either unaware of their corresponding adult institution's policy (62%) or had a counterpart adult program with a policy against pregnancy post HT (12%). While many clinicians feel pregnancy is feasible in pediatric HT recipients, there remains significant practice variation. Few pediatric programs have a policy regarding pregnancy post HT. Future efforts to provide consistent messaging between adult and pediatric HT programs regarding the feasibility and care of post HT pregnancy are warranted.

Impact of co-morbidities on survival after heart transplant in females of childbearing age: analysis of the International Society for Heart and Lung Transplantation (ISHLT) Registry

Abstract Background Data on life expectancy specific to female heart transplant (HT) recipients of reproductive age are lacking, but are needed to inform shared decision making at the time of pre-conception counseling. We analyzed the ISHLT registry for post-transplant survival and studied the impact of co-morbidities in women of childbearing age. Methods Female HT recipients reported to the ISHLT registry who were aged 15–45 yrs at time of HT were included in this retrospective analysis. Primary outcome was post-transplant survival. Secondary outcomes included the impact of co-morbidities on conditional survival at 5, 10 and 15 years. Results Of 121,501 HT recipients (Jan 1992–June 2018), 30,179 (24.8%) were women. 9,229 (7.6%) were 15–45 yrs at time of HT. Overall median post-transplant survival was 15.2 yrs. Diabetes mellitus (DM) and/or severe chronic kidney disease (CKD) at HT adversely impacted long-term survival (Figure 1). Co-morbidities including cardiac allograft vasculopathy (CAV), DM and CKD negatively impacted 5yr and 10yr conditional survival, individually as well as a combination (Figure 2). 15yr conditional survival confirmed the negative impact of DM and CKD, while CAV did not reach statistical significance. Conclusion Female HT recipients of childbearing age have favorable survival post-HT. Conditional survival at 5 and 10 yrs is negatively impacted by CAV, DM and CKD. The quantification of survival outcomes after heart transplant in women of childbearing age may improve counseling as part of pre-conception informed decision making. Funding Acknowledgement Type of funding sources: None.

217.3: Differences in Short-term and Medium-term Prognosis Between Female and Male Heart Transplant Recipients: Analysis of More Than 20 Years in a Single Center in Argentina

217.3: Differences in Short-term and Medium-term Prognosis Between Female and Male Heart Transplant Recipients: Analysis of More Than 20 Years in a Single Center in Argentina

Heart Transplantation for Peripartum Cardiomyopathy: Outcomes Over 3 Decades

BackgroundThis study evaluated trends and outcomes of patients undergoing heart transplantation for peripartum cardiomyopathy (PPCM) over the past 3 decades. MethodsThe United Network for Organ Sharing registry was used to identify patients undergoing isolated heart transplantation between 1987 and 2020. Patients were stratified by the decade of transplantation. Overall survival was compared using Kaplan-Meier analysis, and risk-adjustment was performed using Cox proportional hazards modeling. ResultsA total of 76 009 heart transplantations occurred in the study period, including 20 352 female patients and 809 female patients with PPCM. The frequency of transplantation for PPCM increased over the study period (P = .015). Among female patients, PPCM was significantly associated with 1-year mortality compared with nonischemic cardiomyopathy (hazard ratio, 1.38; 95% CI, 1.11-1.69; P = .004). Among patients with PPCM, Black and Hispanic heart transplant recipients had increased 1-year posttransplant mortality risk compared with White recipients. On Kaplan-Meier survival analysis, early and midterm survival was significantly worse in patients with PPCM compared with other female patients. The 5-, 10-, and 15-year survivals in patients with PPCM were 66.5%, 49.0%, and 40.2% compared with 74.3%, 56.0%, and 37.5% in female heart transplant recipients with other heart failure diagnoses, respectively (P < .001). Survival improved significantly in patients who underwent heart transplantation for PPCM in the latest decade from 2010 to 2020 compared with earlier decades (P < .001), and this improvement was most marked for Black recipients. ConclusionsPatients who underwent heart transplantation for PPCM have a significantly elevated risk for 1-year mortality compared with other female transplant recipients. However, survival among these patients has improved in the last decade, particularly for Black transplant recipients.

Difference in absolute lymphocyte count among male and female heart transplant recipients.

The impact of sex on immune composition in the setting of solid organ transplantation is unknown. Immunocompetent men and women have quantitative differences in multiple markers of immunity, including lymphocyte subsets. Lymphocytes are of particular interest given the routine use of medications targeted at cell-mediated immunity. The objective of this retrospective cohort study was to compare absolute lymphocyte count (ALC) measurements of male and female heart recipients immediately before, and 1month after, transplantation. Data was collected on 375 adult recipients (104 female and 271 male) from 2000 to 2018 at a single center. Mean ALC was compared using Student's t-test. Women had higher mean ALC both at baseline (female 1.6×103 cells/μl vs. male 1.3×103 cells/μl; P<.001) and at 1month post-transplantation (mean 1.2×103 cells/μl vs. .8×103 cells/μl; P<.001). This finding could have important implications for sex-based differences in predisposition to rejection or response to infection or vaccination.

Successful pregnancy outcome in patient with cardiac transplantation

Abstract Objectives The population of female heart transplant recipients of reproductive age is increasing and pregnancy follow-up of these patients is important. Case presentation A 30-year-old patient who had a heart transplant due to viral myocarditis became pregnant spontaneously. A close follow-up by a multidisciplinary team allowed a normal pregnancy without maternal or fetal complications and the delivery of a healthy infant. Conclusions Successful pregnancy outcomes are possible in women who had a heart transplant. Careful and close surveillance by a multidisciplinary team is mandatory.

Similar Long-term Survival in Men and Women Despite Lower Risk Profile in Women in the Contemporary Heart Transplantation Era

Background Women continue to be under-represented as heart transplant (HT) recipients. Past studies on survival rates following HT and gender have suggested conflicting data. We compare long-term survival between male and female HT recipients in the contemporary heart transplantation era from 2000-2018 using novel methods. Methods We identified adult HT recipients between 2000 and 2018 in the Scientific Registry of Transplant Recipients. Men and women were matched using overlap propensity score weighting. We compared 10-year survival with the Kaplan-Meier method. We constructed doubly-robust Cox proportional hazards regression models to determine the risk-adjusted influence of gender on survival. Models were adjusted for recipient and donor characteristic including IMPACT score and donor-recipient predicted heart mass (PHM) ratio. The proportionality assumption was tested by inspection of Shoenfeld residuals with covariates being converted to time-varying if significant. Results We included 36,606 HT recipients. When compared with men, women tended to be younger, have fewer comorbidities, higher PRA, larger IMPACT score and donor-recipient PHM ratio. Unadjusted 10-year estimated survival was similar between men and women (Figure). After risk-adjustment, women had a similar risk of 10-year survival than men (HR 0.94, 95% CI 0.82-1.02; p=0.0974). When comparing between men and women at 1 (p Conclusions In this contemporary cohort of HT recipients, women had similar long-term survival to men despite an overall lower risk profile and greater likelihood to receive a size mismatched heart.

Gender and Racial Disparities in Pediatric Heart Transplantation in the Current Era: A UNOS Registry Analysis

In adults, female (F) and African American (AA) heart transplant (HT) recipients have higher waitlist (WL) and post-transplant (PT) mortality. Our study aims to evaluate gender and racial disparities in pediatric recipients and its effect on survival in the WL and PT period in the current era. Pediatric (<18 years, n=3257) pts listed for HT from 2012-2017 were included. Clinical characteristics at listing, including VAD use were compared between different gender and ethnicity. Kaplan-Meier curves were generated to compare survival in the WL and PT period. 1435 (44%) F were listed for HT during the study period. Compared to males (M), F recipients listed for HT were younger, more likely AA (19 vs. 22%), and cardiomyopathy [CMP] (41.3 vs. 51.4%) [p<0.01 for all]. There were no differences, however, in the use IV inotropes, ventilation, ECMO and dialysis use; Status 1A listing or median WL times [p>0.05 for all]. 663 (20%) AA HT candidates were listed. Compared to Caucasian, AA recipients more likely had CMP (41.3 vs. 49.5%), listed Status 1A (68.7 vs. 72.9%), had renal dysfunction (47.4 s. 53.4%) and were on Medicaid (33.3 vs. 65%) [p<0.01 for all]. While the incidence of IV inotrope use and ICD was lower in AA recipients (50 vs. 48.6% and 9 vs. 5.8% respectively), there was no difference in the incidence of VAD, ECMO, mechanical ventilation and dialysis use. AA recipients had shorter WL times (median 2.1 vs. 2.5 months). While unadjusted WL and PT survival was similar between different gender and race (Figure), multivariate analysis revealed higher waitlist mortality for females [HR 1.2 (1.0-1.5); p=0.04] and African American [HR 1.3 (1.0-1.7); p=0.02] recipients. However, no such difference was seen in post-transplant survival in female [HR 0.9 (0.7-1.2), p=0.35] or AA [1.3 (HR 0.9-1.8), p=0.2] recipients. In the current era, pediatric heart transplant recipients who are F and AA continue to have higher waitlist mortality. Such disparities do not exist post-transplant.

Pregnancy outcomes in heart transplant recipients

The population of female heart transplant recipients of reproductive age is growing, and counseling regarding reproductive decisions is important. We describe maternal and fetal outcomes of pregnancy in the Transplant Pregnancy Registry International. Data regarding pregnancies between 1987 and 2016 were collected via questionnaires, phone interviews, and medical records review. Demographics, comorbidities, changes in immunosuppressive regimens, rejection episodes during pregnancy, data on maternal retransplants, and deaths were recorded. A total of 91 patients reported 157 pregnancies. Mean maternal age at conception was 27 ± 5.6 years. The most common indications for transplant were congenital heart disease (22%) and viral myocarditis (18%). Average transplant to conception interval was 7 ± 6.1 years. Immunosuppression was calcineurin inhibitor-based in almost all patients, with 20% of recipients taking mycophenolic acid (MPA) while pregnant. Complications during pregnancy included pre-eclampsia (23%) and infections (14%). Rejection was reported during 9% of pregnancies and within 3 months postpartum in 7%. Livebirths occurred in 69%, with no neonatal deaths. Miscarriages occurred in 26% of pregnancies, 49% of which had MPA exposure. Mean follow-up post pregnancy was 8.9 ± 6.5 years. At last follow-up, 30 recipients had died, an average of 9.4 ± 6.2 years after pregnancy. The most common causes included allograft vasculopathy and rejection. This is the largest reported series of pregnancies in heart transplant recipients and demonstrates that two thirds of pregnancies reported are successful. MPA exposure is associated with increased risk of teratogenicity and miscarriage. Pre-pregnancy counseling should include discussions of risk of MPA exposure, rejection, graft dysfunction, and maternal survival.

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Pregnancy Outcomes in 91 Female Heart Transplant Recipients

Pregnancy Outcomes in 91 Female Heart Transplant Recipients

Hormone Therapy in Women After Heart Transplantation

BackgroundHormone therapy (HT) for menopausal women has been controversial regarding cardiac outcomes and adverse effects. Studies suggest that HT may cause increase in heart disease, stroke, and cancer. The use of HT in heart transplantation has not been firmly established. MethodsThe records of 356 female heart transplant recipients, undergoing transplantation from 1994 to 2011, were reviewed. We found 19 patients after age 35 years who were initiated on HT for noncontraceptive purposes. These patients were compared 1:3 with a contemporaneous control group matched for age, sex, era, and time after heart transplantation (paired for time from transplantation to initiation of HT). We assessed for subsequent 5-year survival, freedom from cardiac allograft vasculopathy (CAV; stenosis ≥30%), freedom from nonfatal major adverse cardiac events (NF-MACE; myocardial infarction, heart failure, percutaneous cardiac intervention, stroke, and need for pacemaker/defibrillator), and subsequent 1-year freedom from any-treated rejection. Additionally, we compared significant adverse effects of HT between groups. ResultsHT patients compared with control subjects revealed no significant difference in subsequent 5-year survival (79% vs 75%; P = .66), freedom from CAV (90% vs 88%; P = .85), or NF-MACE (90% vs 93%; P = .65). There was also no significant difference in subsequent 1-year freedom from any-treated rejection between the groups. Other adverse effects of HT including subsequent 5-year incidence of thrombosis (pulmonary embolus), malignancy, and stroke were also similar to control subjects. ConclusionsHT is not associated with poor outcome or adverse effects in female heart transplant patients after age 35 years. However, a larger cohort of patients is necessary to confirm these observations.

Pregnancy Outcomes in Female Heart Transplant Recipients with the Initial Diagnosis of Congenital Heart Defect

Purpose The purpose of this study was to describe pregnancy in female heart recipients who received their transplant due to a congenital defect. Methods and Materials Data were collected by the National Transplantation Pregnancy Registry (NTPR) via questionnaires, phone interviews, and medical records. Results There are 65 heart recipients with 113 pregnancies reported to the NTPR to date. Of these, 14 recipients (22 pregnancies) had an initial diagnosis of a congenital heart defect (hypoplastic left heart syndrome 4, transposition of the great vessels 3, tricuspid atresia 2, septal defect 1, fibroelastosis 1, two-chambered heart 1, and other 2). Mean age at first transplant was 14±10.7 yrs. The transplant to conception interval was 4.7±3.4 yrs. Immunosuppression during the pregnancies was calcineurin-inhibitor based with mycophenolic acid product (MPA) exposure in 11. Outcomes were 7 miscarriages (all MPA exposure) and 15 live births with a mean gestational age of 36.7±2.4 wks and a mean birthweight of 2586±546 g. There were 5 children with birth defects: 1 with duodenal atresia, Tetralogy of Fallot and atrioventricular canal defect (MPA exposure), 1 with facial defects (MPA exposure), 1 pectus excavatum, 1 atrial septal defect, and 1 long QT syndrome. Comorbid conditions during pregnancy: hypertension 7, preeclampsia 4, and infection 3. One recipient had mild rejection during pregnancy treated with an increase in oral prednisone. One recipient was retransplanted 12 yrs post-delivery but subsequently died, and 13 recipients reported adequate graft function. Conclusions Female heart transplant recipients born with congenital heart defects have reported successful pregnancies with a majority reporting adequate graft function postpartum. MPA exposure in this group confirms increases in miscarriages and birth defects. The higher frequency of birth defects in the offspring not exposed to MPA in utero in this group warrants further study.

Trichodysplasia Spinulosa-A Rare Complication in Immunosuppressed Patients

Immunosuppression is necessary in a large number of conditions to modify immune responses and control disease severity. It is a vital part of treatment regimes following organ and bone marrow transplants. However, the use of immunosuppressive drugs has been shown to cause infections with common and unusual pathogens. We present the case of a 5-year-old female heart transplant recipient. Nine months after the transplant, she developed a tender acneiform eruption on her face consisting of numerous small yellowish to pink papules and pustules. Many of the lesions had a central, firm, small spinulous excrescence or a central dell. Histopathology demonstrated abnormal maturation of the hair follicles, nucleated eosinophilic cells with trichohyalin granules. The clinical presentation and histological features were in keeping with trichodysplasia spinulosa, a rare complication in immunosuppressed subjects. Treatment trials included reduction of immunosuppression combined with topical and oral retinoids, topical acyclovir, and oral valganciclovir with limited success.

83: Outcomes of female heart transplant recipients bridged to transplantation with a ventricular assist device

83: Outcomes of female heart transplant recipients bridged to transplantation with a ventricular assist device

Physical Activity Patterns in Heart Transplant Women

Maintaining regular, long-term physical activity is critical to achieve favorable effects of heart transplantation. Yet, at present, little is known about the physical activity patterns of transplant recipients, especially women. The study was conducted to (1) describe levels and types of physical activity using actigraphy and self-report, (2) determine the association between physical activity and sociodemographic variables, and (3) assess the relationship between physical activity, quality of life (QOL), and relevant health indicators (hypertension, hyperlipidemia, and obesity) among female heart transplant recipients. Twenty-seven women (average age, 57 +/- 13 years, primarily Caucasian [82%], retired [89%], married [67%], average time since transplant 2.1 +/- 1.3 years) from a single heart transplant facility were asked to report amount and types of physical activity and overall QOL and wear an actigraph for 1 week to measure physical activity level. Physical activity levels by actigraphy averaged 280,320 +/- 52,416 counts for the week (range, 206,784-354,144); self-reported physical activity level on a 0 to 10 scale was 4.3 +/- 0.37 (range, 0-7). The actigraph and self-reported measures were significantly correlated (r = 0.661, P = .000). It was found that women were more likely to engage in household tasks and family activities than occupational activities or sports. Significant differences in physical activity (F = 6.319, P = .006) were observed in participants who reported fair (n = 13), good (n = 9), and very good (n = 5) overall QOL. The only demographic factor associated with physical activity was age; younger women were more active than older women (r = -0.472, P = .013). A negative correlation was found between levels of physical activity and presence of hypertension, hyperlipidemia, and obesity. It was found that a majority of female transplant recipients remains sedentary. Given the association between physical activity and overall QOL and relevant health indicators, measures to enhance physical activity need to be developed and tested; these strategies may be beneficial in improving overall outcomes.

Does Gender Influence the Likelihood or Types of Complications Following Cardiac Surgery?

Over 410,000 cardiac surgeries are performed in American women each year. Women having coronary artery bypass graft (CABG) and valve surgery do so at an older age and with more cardiovascular risk factors than men. Women's smaller body size may also increase risk by increasing the technical difficulty of surgical procedures. Female CABG patients appear to have higher perioperative mortality and cardiac morbidity, although studies of neurologic outcomes in female CABG patients have produced equivocal findings. Women undergoing CABG tend to consume more hospital resources than men do in terms of blood transfusion, mechanical ventilation, and length of intensive care unit and overall hospital stay. With regard to valve surgery, women appear to have worse outcomes than men if the surgery is combined with a CABG operation. Women and men undergoing isolated aortic valve surgery have similar mortality, but little is known about gender differences in mitral and tricuspid valve surgery outcomes. Women who require heart transplantation tend to have idiopathic cardiomyopathy rather than the ischemic cardiomyopathy that is more common in male heart transplant candidates. Although female heart transplant recipients seem to have a stronger immunologic response after transplantation, which manifests in more frequent acute rejection episodes, it is not clear whether this increases women's mortality risk. Men appear to have a greater incidence of posttransplant vasculopathy than women. Further research is needed to identify risk factors for perioperative morbidity and mortality in women undergoing cardiac surgery and to develop medical interventions to mitigate these risks.

Acquired Glanzmann's thrombasthenia as part of multiple-autoantibody syndrome in a pediatric heart transplant patient

Although advances in immunosuppressive therapy have allowed prolonged patient survival, immune dysregulation observed in these patients has increased. We report an 11-year-old female heart transplant recipient in whom Glanzmann thrombasthenia was identified as part of a “multiple autoantibody syndrome” manifesting sequentially as autoimmune hemolytic anemia, thrombocytopenia, and neutropenia.