End-stage Heart Disease Research Articles

Prevalence and clinical significance of left ventricular thrombus discovered by pathological examination in explanted hearts of patients with end-stage cardiomyopathy

Abstract Objective We sought to determine the prevalence of anatomic LV thrombus detected by pathological examination of explanted hearts in patients with end-stage cardiomyopathy (CM) who have undergone heart transplantation, and to examine the relationship between anatomic LV thrombus missed by cardiac imaging and thromboembolic events. Methods and results A total of consecutive 148 explanted hearts from patients (44 years; 80% were men) undergoing heart transplantation were examined. The most common etiology of end-stage heart failure was dilated CM (53%). Of 148 explanted hearts, LV thrombus was present in 19 patients/hearts (13%). Excluding patients with ischemic CM (n=7), LV thrombus was present in 8 DCMs (9%), 1 genetic associated with LV noncompaction (100%), 2 hypertrophic CM (25%), and 1 arrhythmogenic CM (14%). None of patients with cardiac sarcoidosis (n=5) had LV thrombus. Of these patients, 11 (58%) received anticoagulants with favorable numbers of time in therapeutic range. No patient in the cohort had history of thromboembolic event before heart transplantation. Only 11 patients (26 %) with pathological evidence of LV thrombus had LV thrombus detected by previous echocardiograms (median time difference from echocardiogram to heart transplantation = 170 days). Six of 19 patients with anatomic LV thrombus had undergone cardiac MRI; LV thrombus had been detected in 2 patients (33%). The most common site of missed LV thrombus was LV cavity (where thrombi did not attach to any particular LV endocardial surface) followed by LV apex (Figure). Conclusion The prevalence of LV thrombus found by pathological examination in end-stage heart diseases was 13 % despite anticoagulation in most patients. However, the presence of these thrombi did not cause any serious thromboembolic events. Anatomic LV thrombi were missed by echocardiography/cardiac MRI in approximately 70% of patients. Genetic associated LV noncompaction and HCM were the most 2 prevalent CMs with anatomic thrombi, while none of patients with cardiac sarcoidosis had evidence of LV thrombus. Further study in thromboembolic milieu involving endocardial surface in specific type of CM may be needed.

Enhancing Safety in Left Ventricular Assist Device Implantation: Laparoscopic Technique for Driveline Tunneling.

Advancements in left ventricular assist device (LVAD) technologies have significantly lowered morbidity and mortality in patients with end-stage heart disease; however, they still carry significant risks. Though infrequent, intraabdominal injury during driveline tunneling can be catastrophic. Laparoscopic visualization can reduce these risks, especially benefiting patients with lower body mass indexes and thin abdominal walls. We present two cases of laparoscopic driveline tunneling. The laparoscopic procedure begins poststernotomy and preheparin administration to mitigate bleeding risks. Supraumbilical port placement is performed for optimal direct visualization of the abdominal space for accurate driveline tunneling. It involves careful management of insufflation pressure to prevent hemodynamic collapse by restricting venous return. This approach ensures that the driveline is positioned correctly without injury to any intraabdominal structures.

Implantation of a permanent pacemaker following orthotopic heart transplantation: a systematic review and meta-analysis.

Orthotopic heart transplant (OHT) is among the final armamentariums for end-stage heart disease. Many patients who have had OHT require a post-transplant permanent pacemaker (PPM) implantation due to an abnormal conduction system. We aimed to evaluate the risk of mortality and acute rejection in patients with OHT who had received PPM compared to patients without PPM and to determine predictors for PPM placement in this population. We comprehensively searched for studies from MEDLINE, EMBASE, and Cochrane databases from inception to September 2023. Inclusion criteria focused on patients who had undergone OHT and PPM implantation post-transplant. Data from each study were combined using a random-effects model. Results were expressed as relative risk (RR) or odd ratios (OR) with a 95% confidence interval (CI). A total of 9 studies were included in this meta-analysis incorporating a total of 54,848 patients (3.3% had PPM). The pooled all-cause mortality rate among patients with PPM post-OHT was 26% (95% CI: 19-33%, I2 = 1%). There were no differences between post-heart transplant patients with PPM and those without PPM in risk of all-cause mortality (RR 0.76, 95% CI: 0.43-1.34; I2 = 45%) and acute rejection (RR 1.22, 95% CI: 0.74-2.00, I2 = 59%). Bi-atrial anastomosis was associated with an increased risk of PPM implantation post-OHT (OR 7.74, 95% CI: 3.55-16.91, I2 = 0%), while pre-OHT mechanical circulatory support (MCS) was associated with a decreased risk of PPM implantation post-OHT (OR 0.45, 95% CI 0.27-0.76, I2 = 0%). There were no significant differences in all-cause mortality or acute rejection between post-OHT recipients who required PPM compared to those who did not receive PPM. Further, bi-atrial anastomosis portended the need for PPM implantation, while MCS was associated with a decreased occurrence of PPM.

Pediatric Combined Heart-liver Transplantation: A Single-center Long-term Experience.

Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients. We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7-17 y who underwent CHLT. Most patients were surgically palliated via Fontan procedure pretransplant (n = 6), and all had evidence of advanced fibrosis or cirrhosis before transplant. The 30-d mortality was 14.3% (n = 1, multiorgan failure). During the follow-up period, 1 patient developed acute heart rejection which required treatment and 2 developed acute liver rejection. In all cases, rejection was successfully treated. Two patients developed acute heart rejection which did not require treatment (grade 1R). No patients developed chronic or refractory rejection. No patients developed allograft coronary artery vasculopathy. CHLT remains a rarely performed treatment for pediatric patients with end-stage heart and liver disease, but our long-term data suggest that this treatment strategy should be considered more frequently.

Ethics of abortion in transplantation.

The controversial medical procedure of abortion is the subject of this article. It argues that for transplant patients, including recipients, abortion is ethical. In June 2022, the United States Supreme Court overturned the long-standing decision of Roe v. Wade. This decision has led to a socio-legal environment where obtaining an abortion is impossible for some patients. However, the moral position relating to patients who have undergone transplants or are on a waiting list has been largely overlooked. End-stage renal, liver, and heart disease presents a hazardous situation for pregnancy, posing risks to both the fetus and the pregnant person. The abortion procedure is medically safer and allows a patient to proceed with a transplant. Limiting access to abortion or preventing it altogether will have a significant negative impact on transplant patients. The ethical analysis of abortion can be likened to compelling a relative or loved one of a transplant recipient to donate an organ to their family member or loved one. This article emphasizes the importance of maintaining the legal availability of abortion for transplant patients. Allowing abortions in transplant patients upholds ethical parity, as seen in the analogous situation of live organ donation.

Highly sensitized patients listed for heart after liver transplantation with or without domino

For patients with end stage heart disease and borderline hemodynamics, high HLA allosensitization presents a barrier for heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant (HALT-D) on a single patient without liver disease. We describe this patient's course to date as well as four subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.

Surgical Technique of Donation after Circulatory Death using Normothermic Regional Perfusion

Heart transplantation (HT) is the gold standard treatment of end-stage heart disease. Waitlist mortality remains high due to a shortage of available donor organs. Donation after circulatory death (DCD) has shown potential to increase transplant volumes by 15-20%%. Resuscitation of the organs after circulatory death can be performed ex vivo using machine perfusion or in situ using either extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB). Thoracoabdominal normothermic regional perfusion (TA-NRP) entails reperfusing the heart in-situ after circulatory death. It also involves total body reperfusion under physiological conditions, correction of metabolic abnormalities, and allows unloading of the left ventricle to facilitate myocardial recovery. After weaning off support, direct visual and hemodynamic assessment of heart function is possible. Safe and expeditious establishment of cardiopulmonary bypass after death is the key to success of this technique. Here, we review the history of donation after circulatory death, our protocol and surgical technique of establishing TA-NRP with cold static preservation, and briefly describe the outcomes after DCD heart transplantation.

The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [18F]FDG Imaging

PurposeLeft ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection.ProceduresSeventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard.ResultsNine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555–0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571–0.964), respectively.ConclusionsVolumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.

Postoperative pain management after thoracic transplantations.

Heart and lung transplantation evolution marked significant milestones. Pioneering efforts of Dr Christiaan Barnard with the first successful heart transplant in 1967, followed by advancements in heart-lung and single-lung transplants by Drs Bruce Reitz, Norman Shumway, and Joel Cooper laid the groundwork for contemporary organ transplantation, offering hope for patients with end-stage heart and pulmonary diseases. Pretransplant opioid use in heart transplant recipients is linked to higher mortality and opioid dependence posttransplant. Effective pain control is crucial to reduce opioid-related adverse effects and enhance recovery. However, research on specific pain management protocols for heart transplant recipients is limited. In lung transplantation effective pain management is crucial. Studies emphasize the benefits of multimodal strategies, including thoracic epidural analgesia and thoracic paravertebral blocks, to enhance recovery and reduce opioid use. Perioperative pain control challenges in lung transplantation are unique and necessitate careful consideration to prevent complications and improve outcomes. This review emphasizes the importance of tailored pain management in heart and lung transplant recipients. It advocates for extended follow-up and alternative analgesics to minimize opioid dependency and enhance quality of life. Further high-quality research is needed to optimize postoperative analgesia and improve patient outcomes.

Hip replacement in a heart transplant patient: a case report

Solid organ transplantation is considered the most effective treatment for endstage heart, lung, pancreatic, liver, and kidney diseases. The increasing number of transplants performed, and long-term survival of recipients have contributed to an increase in the diagnostic rate of non-transplant-related diseases.Heart transplant patients are at increased risk of complications when undergoing elective or emergency surgery. We report a case of hip replacement in a young man after orthotopic heart transplantation.

Speckle-Tracking Echocardiography in Right Ventricular Function of Clinically Well Patients with Heart Transplantation.

Heart transplantation (HT) is the mainstream therapy for end-stage heart disease. However, the cardiac graft function can be affected by several factors. It is important to monitor HT patients for signs of graft dysfunction. Transthoracic echocardiography is a simple, first-line, and non-invasive method for the assessment of cardiac function. The emerging speckle-tracking echocardiography (STE) could quickly and easily provide additive information over traditional echocardiography. STE longitudinal deformation parameters are markers of early impairment of ventricular function. Although once called the "forgotten ventricle", right ventricular (RV) assessment has gained attention in recent years. This review highlights the potentially favorable role of STE in assessing RV systolic function in clinically well HT patients.

Scoping Review of Wounds in Hospitalized Adults with COVID-19 Over the First Three Years of the Pandemic.

To synthesize the literature on skin failure and pressure injuries among hospitalized patients with COVID-19. An electronic literature search using relevant keywords and controlled vocabulary was conducted in March 2023 on MEDLINE/PubMed, Embase, and CINAHL. Manual citation searches of included articles and grey literature, including the Wound, Ostomy, and Continence Nurses Society website were performed. Articles published in English between 2020 and April 2023 were considered. Articles were included if they reported on COVID-19 positive hospitalized adults with wounds that were not present upon admission. A total of 31 articles met these criteria. Covidence was used to extract the data and was reviewed by multiple team members. Of the 31 studies, 27 reported new onset skin lesions during hospitalization. Wounds were classified as pressure injuries, skin failure, livedo racemosea and/or, retiform purpura, and associated with microvascular thrombosisthrombotic vasculopathy. Most pressure injuries were associated with prone position and affected patients often had multiple comorbidities including hypertension, diabetes mellitus, end-stage renal disease, heart disease, and COPD. Four articles highlighted an increased risk of new onset wounds, and three emphasized the importance of distinguishing deep tissue pressure injuries from ischemic-related lesions in patients with COVID-19. The evidence suggests an increased risk of ischemic lesions and pressure injuries (PI) in patients with COVID-19 infection. This phenomenon may have inflated the numbers of PI during the pandemic and adversely affected nursing quality measures in acute care environments.

Influence of cardiac diagnosis on outcomes of pediatric heart-lung transplantation.

Pediatric Heart-lung transplant (HLTX) is performed for endstage congenital heart disease (CHD) with irreversible pulmonary hypertension or non-congenital heart disease (NCHD) with end-stage heart and lung disease. CHD could influence the outcomes of HTLX due to increased complexity of the operation as compared to NCHD. In this study we evaluated the influence of cardiac diagnosis on outcomes of pediatric HTLX. The UNOS database (1987-2022) was queried for primary HTLX in patients <18years. The data were extracted for demographics, pretransplant characteristics, post-transplant outcomes, and analyzed for the impact of cardiac diagnosis on post-transplant outcomes. Standard statistical tests were used. Survival was compared using the Kaplan-Meier method. Ninety of the 213 patients who underwent HLTX had CHD. There were no demographic differences. Heart listing status was similar but with a higher LAS score for NCHD. NCHD had higher pre-operative life support use (mechanical ventilation, inotropes or dialysis) but the use of ECMO as a bridge to transplantation was similar. Wait-list times were longer for CHD. The ischemic times were similar. Post-transplant dialysis, stroke, prolonged mechanical ventilation, and rejection were similar. Survival at 30-days, 1-year, and long-term survival at 17years was similar. Non-survivors at 30-days post-transplant were on life support, used ECMO as a bridge, had lower wait-list times, longer ischemic times and had strokes. Non-survivors at 1-year had similar factors in addition to a higher dialysis use. Cardiac diagnosis had no impact on outcomes after Pediatric HLTX. Patients on life support or ECMO before transplantation were transplanted faster but with lower survival.

The Art of Sleeve Gastrectomy.

Sleeve gastrectomy (SG) has historically evolved from gastroplasty and anti-reflux procedures into one of the most commonly performed primary metabolic surgeries in the United States and worldwide. Initially initiated in the 1980s as part of the duodenal switch procedure, its standalone effectiveness and simplicity have led to increasing popularity globally. The rise in obesity rates transcends age boundaries, alarmingly affecting not only adults but also the younger demographic. This escalating trend is concerning, as it predisposes these populations to numerous future health complications, as well as highlighting the critical necessity for a safe and potent weight loss strategy. Although sleeve gastrectomy carries a higher risk for gastroesophageal reflux disease (GERD) compared to other bariatric procedures, it stands out as a reliable, safe and effective surgical solution for obesity. It is particularly beneficial for adolescents and patients with complex medical comorbidities, including, but not limited to, heart failure and immunocompromisation. It has also served as a bridge for transplants in morbidly obese patients with end-stage heart, liver and kidney disease due to its favorable safety profile.

MicroRNA-22-3p displaces critical host factors from the 5' UTR and inhibits the translation of Coxsackievirus B3 RNA.

Coxsackievirus B3 (CVB3) is known to cause acute myocarditis and pancreatitis in humans. We investigated the microRNAs (miRNAs) that can potentially govern the viral life cycle by binding to the untranslated regions (UTRs) of CVB3 RNA. MicroRNA-22-3p was short-listed, as its potential binding site overlapped with the region crucial for recruiting internal ribosome entry site trans-acting factors (ITAFs) and ribosomes. We demonstrate that miR-22-3p binds CVB3 5' UTR, hinders recruitment of key ITAFs on viral mRNA, disrupts the spatial structure required for ribosome recruitment, and ultimately blocks translation. Likewise, cells lacking miR-22-3p exhibited heightened CVB3 infection compared to wild type, confirming its role in controlling infection. Interestingly, miR-22-3p level was found to be increased at 4 hours post-infection, potentially due to the accumulation of viral 2A protease in the early phase of infection. 2Apro enhances the miR-22-3p level to dislodge the ITAFs from the SD-like sequence, rendering the viral RNA accessible for binding of replication factors to switch to replication. Furthermore, one of the cellular targets of miR-22-3p, protocadherin-1 (PCDH1), was significantly downregulated during CVB3 infection. Partial silencing of PCDH1 reduced viral replication, demonstrating its proviral role. Interestingly, upon CVB3 infection in mice, miR-22-3p level was found to be downregulated only in the small intestine, the primary target organ, indicating its possible role in influencing tissue tropism. It appears miR-22-3p plays a dual role during infection by binding viral RNA to aid its life cycle as a viral strategy and by targeting a proviral protein to restrict viral replication as a host response.IMPORTANCECVB3 infection is associated with the development of end-stage heart diseases. Lack of effective anti-viral treatments and vaccines for CVB3 necessitates comprehensive understanding of the molecular players during CVB3 infection. miRNAs have emerged as promising targets for anti-viral strategies. Here, we demonstrate that miR-22-3p binds to 5' UTR and inhibits viral RNA translation at the later stage of infection to promote viral RNA replication. Conversely, as host response, it targets PCDH1, a proviral factor, to discourage viral propagation. miR-22-3p also influences CVB3 tissue tropism. Deciphering the multifaced role of miR-22-3p during CVB3 infection unravels the necessary molecular insights, which can be exploited for novel intervening strategies to curb infection and restrict viral pathogenesis.

Towards Allograft Longevity: Leveraging Omics Technologies to Improve Heart Transplant Outcomes.

Heart transplantation (HT) remains the optimal therapy for patients living with end-stage heart disease. Despite recent improvements in peri-transplant management, the median survival after HT has remained relatively static, and complications of HT, including infection, rejection, and allograft dysfunction, continue to impact quality of life and long-term survival. Omics technologies are becoming increasingly accessible and can identify novel biomarkers for, and reveal the underlying biology of, several disease states. While some technologies, such as gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), are routinely used in the clinical care of HT recipients, a number of emerging platforms, including pharmacogenomics, proteomics, and metabolomics, hold great potential for identifying biomarkers to aid in the diagnosis and management of post-transplant complications. Omics-based assays can improve patient and allograft longevity by facilitating a personalized and precision approach to post-HT care. The following article is a contemporary review of the current and future opportunities to leverage omics technologies, including genomics, transcriptomics, proteomics, and metabolomics in the field of HT.

Abstract 16289: Functional Status Improves Following Heart Transplantation for Most Patients and Functional Status at One Year Predicts Five-Year Survival

Introduction: Heart transplantation is a critical treatment for end-stage heart disease, with the goal of improving both length and quality of life. We investigated predictors of functional status improvement following transplant and the impact of functional status at 1 year on survival. Methods: We used data from the Scientific Registry of Transplant Recipients on 34,649 U.S. adults who received a heart transplant from Jan. 2006 - Jul. 2020. Functional status was measured using the Karnofsky Performance Scale (KPS; 0-100%). Linear regression with stepwise selection was used to identify predictors of change in KPS from listing to transplant, and from transplant to 1 and 5 years post-transplant. Kaplan Meier curves with log-rank testing was used to compare 5-year survival between patients with poor (≤50%) versus non-poor (&gt;50%) KPS at 1 year. Results: Mean KPS was low at listing (47.9%, SD 22.4%) and discharge following transplant (45.6%, SD 24.1%). At 1-year post-transplant, the mean KPS increased to 85.8% (SD 17.7%), which was stable at 5 years (Figure). There was a small difference in KPS at 1 and 5 years based upon KPS at listing (p&lt;0.0001). After adjusting for KPS at transplant and transplant center, predictors of the magnitude of KPS change from transplant to 1 year included insurance type, diabetes, hypertension, prior cardiac surgery, smoking, “1A” waitlist priority, and hospitalization status. Predictors of KPS change from transplant to 5 years included insurance type, diabetes, ventricular assist device use, prior cardiac surgery, sex, and age. Only 5.5% of patients had poor KPS (≤50%) at 1 year. Of these patients, 5-year survival was significantly lower at 72.9% compared to 88.3% among patients with KPS&gt;50% at 1 year (p&lt;0.0001). Conclusions: Functional status is an important outcome following heart transplant and impacts survival. Most patients alive at 1 year have excellent KPS but clinical and social interventions may help optimize KPS among at-risk patients.

High-dimensional profiling of pediatric immune responses to solid organ transplantation

Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼33% of allograft recipients experience acute rejection within the first year after transplant. Our ability to detect early rejection is hampered by an incomplete understanding of the immune changes associated with allograft health, particularly in the pediatric population. We performed detailed, multilineage, single-cell analysis of the peripheral blood immune composition in pediatric solid organ transplant recipients, with high-dimensional mass cytometry. Supervised and unsupervised analysis methods to study cell-type proportions indicate that the allograft type strongly influences the post-transplant immune profile. Further, when organ-specific differences are considered, graft health is associated with changes in the proportion of distinct Tcell subpopulations. Together, these data form the basis for mechanistic studies into the pathobiology of rejection and allow for the development of new immunosuppressive agents with greater specificity.

Current Progress of 3D Bioprinting of Cardiac Tissues

Heart disease is the leading cause of death worldwide. Heart transplants are used when treating end-stage heart disease. The main problem faced by heart transplantation is the scarcity of donors. Therefore, finding a way to replace the donor heart remains a major medical challenge. In recent years, 3D bioprinting has often been used in tissue engineering, and it has achieved results in the preparation of many types of human tissues. Therefore, it is regarded as a promising method for alleviating donor heart scarcity. In this article, we summarize the current research progress of 3D bioprinting of cardiac tissue, and after introducing several 3D bioprinting methods, bioinks, and 3D bioprinting steps for heart tissue, we proposed our perspectives on 3D bioprinting, discussed several current challenges, and analysed the future of development.

Lung Transplant After a Heart Transplant: A Case Report

A heart-lung transplant is considered in patients with end-stage heart and lung disease. However, there is no report of a patient receiving a staged heart transplant followed by a lung transplant. Our case report describes a successful left single lung transplant for idiopathic pulmonary fibrosis 6 years after a heart transplant. This case illustrates that this approach can avoid significantly increased wait time until transplant, and it shows that early interstitial lung disease may not be a contraindication for the heart transplant.