Utilization of the percutaneous left ventricular support as a bridge to heart transplantation across the United States: In-depth UNOS database analysis

To determine the national patterns of Intra-aortic balloon pump (IABP) and Impella (5.5 or 5.0) utilization as a bridge to heart transplantation (HTx) following the


Limitations
Objective: Female sex is a strong risk factor for pulmonary arterial hypertension (PAH), yet males have worse survival.We sought to understand this "sex paradox" by pairing data from the Pulmonary Hypertension Association Registry (PHAR) with epidemiologic modeling.Methods: Adult PAH patients in PHAR were included.Baseline differences were assessed by sex.Survival analysis was performed by sex.Mediation analysis was conducted with Cox proportional hazards regression by comparing the unadjusted hazard ratios for sex before and after adjustment for groups of covariates.The plausibility of collider-stratification bias was assessed by modeling how large an unmeasured factor (U) would have to be to generate the sex-based mortality differences which were observed in PHAR.
Results: Among 1,891 patients included, 75% were female.Women had less favorable hemodynamics, lower 6-minute walk distances (6MWD), more PAH therapies, and worse functional class; however, sex-based differences were less pronounced when accounting for body surface area or expected variability by gender.On multivariate analysis, women had a 48% lower risk of death compared to men (Hazard Ratio 0.52, 95% Confidence interval 0.36 -0.74, p < 0.001).Differences in age, PAH diagnosis, comorbidities, health-related behaviors, social determinants, 6MWD, PAH therapies, and hemodynamics did not fully explain the observed sex-based mortality difference.Modeling found that under reasonable assumptions collider-stratification via an unmeasured upstream factor could account for the observed lower mortality in women.
Conclusions: In this large registry of PAH patients new to a care center, men had worse survival than women despite more favorable baseline characteristics.Collider-stratification bias could account for the observed greater mortality among men.

Investigating the "sex paradox" in pulmonary arterial hypertension: results from PHAR
DesJardin JT, Kime N, Kolaitis N, et al. J Heart Lung Transplant June 2024;43(6):901-910 | DOI: 10.1016/j.healun.2024.02.004 • The increased mortality in men with PAH is a well-documented phenomenon, and is typically attributed to sex-based differences in RV function and remodeling in response to PAH. • This study uses epidemiologic modeling to offer an alternative explanation: that increased mortality in men may be a consequence of factors preceding the PAH diagnosis (collider stratification bias).In other words, men are at lower baseline risk of PAH and therefore those who develop PAH require higher-risk causal pathways compared to women.It may be the higher-risk causal pathway which is associated with subsequent mortality when unaccounted for in registry data.• The authors caution readers about the statistical associations which can be induced when stratifying a diseased population by a strong risk factor for that disease (collider stratification bias), and emphasize the need to account for the causal pathways preceding diagnosis in registry-based studies.
• PHAR does not collect detailed data on medical comorbidities, echocardiography, or cardiac MRI, which prevented a more detailed analysis on sex-based differences in comorbidities or right ventricular structure.

Association between sex and mortality in PAH while accounting for various potential mediating factors
Methods: • Retrospective, single-center analysis of 163 lung transplants performed on VA ECMO support.• Categorization into "very low", "low", "moderate", and "high" dose anticoagulation intensities based on heparin bolus doses.• Comparison of blood product transfusion rates (PRBC, Plt, FFP, cryoprecipitate) and thromboembolic events (anastomotic or intracardiac thrombus, DVT, PE, stroke, etc.) based upon anticoagulation intensity groups. Results: • The "very low" (≤ 2000 units of heparin) dose anticoagulation intensity group demonstrated significantly fewer blood products transfused compared to all other groups of increasing anticoagulation intensity.• Rates of thromboembolic events among anticoagulation intensity groups were similar.• A trend toward lower PGD3 at 72 hours was seen in the "very low" intensity group.
Conclusions: "Very low" intensity anticoagulation strategies for venoarterial support during lung transplantation demonstrated a significant decrease in blood product transfusions and a trend toward lower rates of PGD3 at 72 hours.Rates of thromboembolic events did not vary among the anticoagulation intensity groups.Author's Comments

Impact of anticoagulation intensity on blood transfusion for venoarterial extracorporeal membrane oxygenation during lung transplantation
• Lung transplantation performed on VA ECMO provides excellent physiologic support throughout the operation.• VA ECMO support during lung transplant can be utilized without the need for large amounts of blood products.
• "Very low" intensity anticoagulation immediately prior to cannulation is safe and was associated with fewer blood products transfused compared to higher intensity groups.• A trend toward lower PGD3 at 72 hours warrants further investigation of "very low" anticoagulation intensity.

Limitations
• Single-center, retrospective analysis

Limitations
Objective: Evaluate the outcomes and management of heart transplant (HT) candidates bridged to transplant with temporary mechanical circulatory support (TMCS) experiencing bloodstream infection.
Methods: Single center matched retrospective cohort study of patients bridged to HT with TMCS between 1/1/2013 -3/30/2023.HT candidates on TMCS with bloodstream infection (TMCS-I) were matched 1:4 with candidates on TMCS without infection (TMCS-U) on age and year of HT.Clinical characteristics were compared between groups using Mann-Whitney, chi-square and Fisher's exact test, as appropriate.Time-to-event analyses were performed using Kaplan-Meier survival estimates.Multivariable logistic regression was used to determine factors associated with TMCS-I.
Results: N=136 patients were bridged to HT with TMCS.N=21 (15.4%)TMCS-I were matched with N=84 TMCS-U.Staphylococcus epidermidis was the leading cause of bloodstream infection among TMCS-I, accounting for 57.1% of all cases.The axillary Impella was the most common type of TMCS among TMCS-I.Median time from TMCS implantation to first positive blood culture was 25 days.All TMCS-I were reactivated on transplant list within 48-72 hours of first negative blood cultures.Median duration of intravenous antibiotic therapy was 24 days (IQR 28.3 days).N=2 received suppressive antibiotics post-HT for 90 days.No TMCS-I patients had recurrent bloodstream infection post-HT.TMCS-I was not associated with decreased post-HT survival.
Conclusions: TMCS-I is not associated with increased risk for mortality or bloodstream infection recurrence after HT.HT may be safe for TMCS-I as soon as blood cultures clear.Methods:

Management and outcomes of heart transplant candidates with bloodstream infection on temporary mechanical circulatory support
• Cross-sectional, observational design.Results: • Of the 35 participants (mean age: 61 years [SD: 10.3], 71.4% male, 71.4% white), 31.4% (n = 11) were classified as nonadherent to their immunosuppression medications.• Higher immediate word recall, indicating better episodic memory, and higher illness coherence scores were associated with not missing doses of medication.• Single center study with a cross-sectional design and a small convenience sample.• Large variation in the time since transplant for the participants in the study.• 3.6 well-formed granulomas per TBBx (range: 1 to >20) • Multinucleated giant cells in 11 TBBx (33.3%) • 1 case with asteroid bodies • 5 cases (15.2%) with prominent lymphoid cuffing.

•
Eichenberger E, Satola S, Gupta D, Daneshmand M, Pouch S. Journal of Heart and Lung Transplant Nov 2023;42(11):1501-1504 | DOI: 10.1016/j.healun.2023.07.011This is the first study providing data on management and outcomes of TMCS-I relative to TMCS-U • Bloodstream infection is a common complication of TMCS and is not associated with increased risk for mortality or bloodstream infection recurrence after HT • Duration of antibiotics is highly individualized and depends on duration of bacteremia, organism, presence of endocarditis, and timing of HT • HT may be safe for patients on TMCS with bloodstream infection as soon as cultures clear • Transplant infectious disease consultants should be involved in the care of patients on TMCS with bloodstream infection • Other transplant centers are encouraged to present their experience with treating bloodstream infections • Additional research is warranted to determine optimal duration of antibiotics and role of antibiotic suppression therapy in TMCS-I • Small number of patients with TMCS-I • Patients who were removed from the waitlist with infection were not evaluated • No TMCS-I had candidemia Legend: Post-heart transplant survival of TMCS-I vs TMCS-purpose of this study was to describe relationships between cognitive function, illness perceptions, and medication adherence among heart transplant recipients.

••
Heart transplant recipients face substantial challenges with the implementation phase of medication adherence.• This study highlights the need for more research that considers the relationships between cognitive impairment and selfmanagement behaviors after heart transplantation.• There is a need for longitudinal evaluations of cognitive function, depression, and medication adherence that utilize more robust measures to further understand these relationships.• The prevalence of mild cognitive impairment after heart transplantation should be considered when designing adherence-promoting interventions.Presented the clinical and histopathologic features of recurrent sarcoidosis diagnosed in posttransplant lung surveillance transbronchial biopsies (TBBx) • 35 patients included, of which 18 (51%) experienced recurrent sarcoidosis posttransplant • Recurrent group had 7 females and 11 males with mean age at recurrence of 51.6 years • Mean time interval from transplant to recurrence was 252 days (22 to 984 d) • No ISHLT A2, A3, or A4 acute cellular rejection; antibody-mediated rejection; or chronic rejection.• 33 surveillance TBBx contained granulomatous inflammation:

•
Clinical and Histopathologic Characteristics of Recurrent Sarcoidosis in Posttransplant Lungs: 25 Years of Experience Lu L, Wein A, Villaneuva A, et al.American Journal of Surgical Pathology Sep 2023; 47(9):1034-1038 | DOI: 10.1097/PAS.0000000000002074Other causes of granulomatous inflammation excluded by review of medications, microbial stains, and microbiology studies.• Background rate of granulomatous inflammation in post-transplant allograft biopsies is only 2.8% at this institution • Tissue diagnosis of recurrent sarcoidosis is gold standard, other reports have used imaging only • This study finds a higher rate of recurrence than other studies • Given the normal allograft survival observed, findings raise questions about the physiology of recurrent sarcoidosis in the lung • Single-site study, which can limit generalizability • Many patients lost to follow-up, so the rate of recurrence is likely underestimated • Very few extra-pulmonary sites of sarcoidosis involvement diagnosed by biopsy, which may artificially increase rates of extrapulmonary involvement

•
Ultimately the reason for increased mortality in men with PAH remains unknown, and although epidemiologic modelling can offer insights and plausible explanations, additional research is required to 1) understand if collider-stratification via an unmeasured up-stream factor can in fact fully account for sexbased mortality differences, and 2) elucidate what that unmeasured factor or factors might be.

May 2024 | Cardiothoracic Surgery Study Highlights Emily Eichenberger, MD, MHS Emory University School of Medicine, Atlanta, GA USA Author's Comments
• Small sample size • Potential variations in operative technique • Potential variations in decisions prompting blood product transfusion • Lack of pre-specified criteria for selecting heparin bolus dosing

•
Higher t-MoCA© total scores, indicating normal cognitive function, and lower depression scores were associated with taking medications on time.•More than 22% (n = 8) of participants scored less than 19 on the t-MoCA©, an indication of mild cognitive impairment.
Conclusions: Cognitive impairment may be more common among heart transplant recipients than what is currently recognized, and specific domains of cognitive function were related to medication adherence after transplantation in this study.

•
Telephone administration of measures.•Use of self-report to measure medication adherence instead of electronic monitoring.