The Impact of a Prior Norwood Procedure on Cardiac Transplantation in Failed Fontan Physiology

Objective:The objective of this study was to compare cardiac transplant operative and postoperative courses of patients with failed Fontan physiology who were initially palliated with a Norwood(FFN)to those without a prior Norwood(FF).Methods:A single-institution retrospective review of all patients with Fontan failure who under-went cardiac transplantation from 2003–2021 was completed-22 underwent prior Norwood(FFN)and 11 did not(FF).Descriptive and inferential statistics were calculated for operative course and patient outcomes.Results:The operative course of the FFN cohort appeared to be more complex(not statistically significant,but clinically relevant)-this group exclusively experienced sternal re-entry events(3 of 22 patients)and concomitant neo-aor-tic reconstruction(6 patients),had a longer duration of surgery(median of 682 min vs.575.5 min),more time on circulatory arrest(median of 25.5 min vs.12.5 min),and more frequent use of open sternal management[50%of patients(11/22)vs.27.3%of patients(3/11)].Postoperatively,these patients underwent more mediastinal explora-tions[other than sternal closure;40.9%of patients(9/22)vs.18.2%of patients(2/11)],spent more time on mechanical ventilation(median of 5 days vs.2 days),had a longer length of stay(median of 30 days vs.19 days),and required more catheter-based re-interventions[22.7%of patients(5/22)vs.9.1%of patients(1/11)].Conclu-sion:Although underpowered,our results suggest that the operative course of FFN patients is more challenging,based mostly on neo-aortic arch issues.In turn,this likely leads to a more complex postoperative course.We are currently collaborating with other institutions to increase the cohort size and power of the study.

Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome

Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.

Activation of Aryl Hydrocarbon Receptor Prolongs Survival of Fully Mismatched Cardiac Allograft

Recent data suggest that activation of aryl hydrocarbon receptor （AhR） by its high-affinity ligand 2,3,7,8-tetrachlorodihenzo-p-dioxin （TCDD） results in expansion of regulatory T （Treg） cells and suppresses the development of autoimmune and allergic diseases in several models. Treg cells have been increasingly documented to suppress allograft rejection and even to establish stable long-term graft acceptance. However, the involvement of TCDD in the regulation of solid organ transplantation rejec- tion is largely unknown. Here, we examined whether activation of AhR with TCDD altered cardiac al- lograft rejection in an allogeneic heart transplant model. Recipient C57BL/6 （H-2b） mice were adminis- trated with a single intraperitoneal injection of TCDD, and the murine cardiac transplant models from BALB/c （H-2d） to C57BL/6 （H-2b） were built 24 h later. The complete cessation of cardiac contractility was defined as the observation endpoint. The effect of TCDD on T-cell proliferation was assessed by mixed lymphocyte reaction （MLR）. Histological and immunohistochemical analyses were performed to estimate the severity of rejection. The phenotype and cytokine profile of lymphocytes were analyzed by flow cytometry and enzyme-linked immunosorbent assay （ELISA）. Activation of AhR remarkably pro- longed the survival of cardiac allografts to more than 20 days. In vitro, TCDD ugregulated the fre- quency of CD4＋CD25＋Foxp3＋ Treg cells and suppressed the proliferation of T lymphocytes. In vivo, the prolonged survival time was associated with increased number of Treg cells in allografls and spleens Furthermore, the secretion of interferon-3, （IFN-3,） and interleukin-17 （IL-17） was reduced to less than 50% of that of the PBS treatment control group by TCDD treatment, whereas IL-10 was elevated to 10-fold of that of the PBS treatment control group. Collectively, our data indicate that activation of AhR with a single dose of TCDD significantly prolonged the survival of fully allogeneic cardiac grafts, and the mechanism underlying this effect might be involved in the induction of Treg cells.

Anesthetic management for the patients with cardiac transplant

With the advancement of medical technique and application of the new immunosuppressant agents, cardiac transplantation has become an effective treatment for end-stage heart disease caused by different reasons. The orthotopic procedure has been performed in many countries nowadays. Whether it is successful or not mainly depends on harvesting the denoted heart, operative technique and perioperative management.

Classic Ehlers-Danlos syndrome and cardiac transplantation-Is there a connection?

Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarring,joint hypermobility with subluxations or dislocations,easy bruisability,hernias,aneurysms and cardiac abnormalities.Advances in genomics technology using next-generation sequencing has led to the discovery of causative genes for connective tissue disorders,hereditary cardiomyopathies and cardiovascular diseases including several genes for connective tissue disorders.A 55 year-old male exhibited thin stretchable skin,atrophic scars,easy bruising,joint pain and dislocations requiring multiple knee surgeries and a Beighton hyperflexibility score of 6 out of 7.He was found to have a heterozygous missense COL5A1 gene variant involving exon 3 at nucleotide c:305T>A with an amino acid position change at p.lle102Asn consistent with classic EDS.He had a heart transplant at 43 years of age due to cardiac failure of unknown cause.This patient with classic EDS is brought to medical attention and should be of interest to cardiologists,heart transplant specialists and surgeons,particularly in individuals with unexplained cardiac failure and then diagnosed prior to surgical intervention to avoid poor wound healing,scarring and other tissue involvement(e.g.,vascular anomalies,blood pressure instability,aneurysms)as components of EDS.

Evaluation of the Management of Hyperlipidemia and Hypertension in an Outpatient Cardiac Transplant Clinic

Background: Allograft coronary artery disease (ACAD) is a common cause of morbidity and mortality post-orthotopic heart transplantation (OHT). ACAD progression may be reduced by modifying cardiovascular risk factors, such as hyperlipidemia and hypertension. We sought to evaluate the management of hyperlipidemia and hypertension among OHT recipients followed in an outpatient cardiac transplant clinic. Objective: The primary objective was to assess the proportion of OHT patients achieving both the recommended LDL target of <2.0 mmol/L and BP targets of <140/90 mmHg (or <130/80 mmHg for diabetics) in an outpatient cardiac transplant clinic. Methods: A cross-sectional retrospective analysis of the medical records of all adult OHT recipients actively followed in our outpatient cardiac transplant between January-March 2009. Results: Of the 193 patients included, both the low-density lipoprotein (LDL) cholesterol and blood pressure (BP) targets were achieved in 111 (57.5%) patients. The LDL target alone was achieved by 140 (72.5%) patients and the BP target alone by 153 (79.3%) patients. Statins were prescribed in 183 (94.8%) patients with a mean LDL of 1.81 mmol/L (±0.55). Angiotensin converting enzyme-inhibitors [ACE-I] (or angiotensin receptor blockers [ARB]) were prescribed in 154 (79.8%) patients, diltiazem in 101 (52.3%) patients, and both in 85 (44.0%) patients, with a mean BP of 124.2/77.8 mmHg (±13.6/8.2). Adverse reactions related to statins, ACE-inhibitors or diltiazem were uncommon and rarely resulted in drug discontinuation. Conclusions: Guideline recommended that LDL and BP targets are achievable in a significant proportion of OHT recipients. The high utilization rates of statins for dyslipidemia and ACE-I (or ARB) and diltiazem for BP were consistent with guideline recommendations for the prevention of ACAD. Despite concerns regarding the potential for pharmacokinetic drug interactions in OHT patients, the reported rates of any drug intolerance to these medications were low in our population.

Clinical analysis of recipients with survival over ten years after cardiac transplantation:a report of 13 cases

Objective To retrospectively analyze clinical management and follow - up of 13 recipients with survival over ten years after cardiac transplantation. Methods Thirteen male recipients underwent orthotopic heart transplantation between August 1995 and June 2001 in our center and received standard immunosuppressive

Orthotopic Heart Auto-Transplantation in a Swine Model

Background and Aim: The porcine heart bears the best resemblance to the human heart and remains the preferred preclinical model for anatomical, physiological, and medical device studies. In an effort to study phenomena related strictly to ischemia reperfusion and donor preservation protocols, it is essential to avoid the immune responses related to allotransplantation. Orthotopic auto-transplantation is a unique strategy to the field of cardiac transplantation for ex vivo experimentation. Nevertheless, auto-transplantation carries its own technical challenges related to insufficient length of the great vessels that are to be transected and re-anastomosed. Methods: A novel method for orthotopic cardiac auto-transplantation in the porcine model was developed and was described herein. Porcine models were used for ex vivo experimentation of a novel device to study ischemia reperfusion injury. Results: A total of five porcine models were used for ex vivo experimentation of a novel device to mitigate ischemia reperfusion injury and determine effects of donor preservation. Modifications to routine cardiac transplantation protocols to allow for successful auto-transplantation are described. Conclusion: Orthotopic cardiac auto-transplantation in the porcine model is a plausible and technically feasible method for reliable study of ischemia reperfusion injury and donor preservation protocols. Here, we describe methods for both direct orthotopic porcine cardiac auto-transplantations as well as a simplified protocol that can be substituted for full surgical auto-transplantation for the studies of preservation of donor hearts.

Mechanical Thrombectomy in Post-Transplant Heart

Coronary allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that is responsible for significant mortality after cardiac transplantation. We report a case of CAV with significant thrombus burden which was managed with mechanical thrombectomy. Both aspiration and mechanical thrombectomy can be safely done in cardiac transplant recipients and may be considered in order to minimize exposure to coronary artery bypass procedure. This is especially valuable in emergency circumstances.

Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant patient

Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients. We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus. Hypertrophy improved when the drug was discontinued and replaced with sirolimus.

Coronary artery disease and heart failure:Late-breaking trials presented at American Heart Association scientific session 2023

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure(HF).The dapagliflozin in patient with acute myocardial infarction(DAPA-MI)trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo,with no difference in cardiovascular outcomes.The MINT trial showed that in patients with acute MI and anemia(Hgb<10 g/dL),a liberal transfusion goal(Hgb≥10 g/dL)was not superior to a restrictive strategy(Hgb 7-8 g/dL)with respect to 30-day all-cause death and recurrent MI.The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy,percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure.The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist,placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year.The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given≥6 months after cardiac transplantation.Providing patients being treated for HF with reduced ejection fraction(HFrEF)with specific out-of-pocket(OOP)costs for multiple medication options at the time of the clinical encounter may reduce‘contingency planning’and increase the extent to which patients are taking the medications decided upon.The primary outcome,which was cost-informed decisionmaking,defined as the clinician or patient mentioning costs of HFrEF medication,occurred in 49%of encounters with the checklist only control group compared with 68%of encounters in the OOP cost group.

Integrated management of cardiac failure:the cardiac failure clinic

The prevalence of the risk factors and the risk of cardiac failure are both increasing in China.This might be the consequence of the changes of the life conditions(emigration to the urban areas,changes in the diet and life style,lack of physical exercise,etc.).The wide range of clinical presentations of cardiac failure(acute or chronic)and of therapeutic approaches(medical or surgical)makes necessary the integration within the same structure of the various experts involved in the diagnosis and the treatment of cardiac diseases.Technologic and human resources required to offer all the options represent a multifaceted commitment which should be focused optimally in dedicated centers.In these centers,collaboration should replace competition between the medical and the surgical cardiac specialists.Development of team work should permit to optimize the cost efficacy of the treatments.Most of all,such a structure will facilitate the translation of innovative therapies between the research centers and clinical facilities.

Effect of donor antigen-trichosnthin conjugate in induction of mouse to rat cardiac xenografting tolerance

Objective To investigate the special effect of donor antigen trichosnthin (TCS) conjugate on depleting the immune reactive cells that respond to xenograft, and thus inducing specific xenograft tolerance. Methods Rat anti mouse antibodies coupled sepharose 4B beads were used to purify mouse H 2 antigens by affinity chromatography. Those purified H 2 antigens were conjugated with TCS by heterobifunctional reagents SPDP [3 (2 pyridyldithio) propionic acid hydroxysuccinimide ester] and 2 IT (2 iminothiolane). The specific inhibition function of Ag TCS to recipient's immune cells was measured in vitro. Ag TCS conjugate (200 μg/kg, iv) was administered to the recipients (rats) 4 days prior to cardiac xenotransplantation of mouse to rat. Results In vitro, the proliferation of immune reactive cells in the recipients pretreated with Ag TCS was inhibited. The Ag TCS conjugate significantly prolonged the cardiac survival time (6.88±1.36 days) compared with cyclosporine A (CsA) group (2.83±0.75 days) (P<0.01). Conclusion Donor Ag TCS conjugate can induce specific tolerance to xenograft.