Requiring Heart Transplantation Research Articles

Left ventricular non-compaction: Underdiagnosed disease with fatal outcomes

Left ventricular non compaction (LVNC) is a type of congenital cardiomyopathy characterized by the presence of prominent intertrabecular recesses that typically affect the apical portion of the left ventricular cavity. These recesses give a distinctive phenotype to the affected myocardium that has been described as “sponge-like”. Devastating complications have been observed in those patients with LVNC, including heart failure requiring heart transplantation in selected cases, life-threatening arrhythmias, thromboembolic events including stroke and transient ischemic attack and sudden cardiac death. This report follows the case of a 62-year-old female patient with recurrent chest pain for several years and extensive negative work and recent echocardiography showed increased left ventricle trabeculations, suspicious for LVNC, later confirmed by cardiac magnetic resonance (CMR).

Cell-based therapy to boost right ventricular function and cardiovascular performance in hypoplastic left heart syndrome: Current approaches and future directions

Congenital heart disease remains one of the most frequently diagnosed congenital diseases of the newborn, with hypoplastic left heart syndrome (HLHS) being considered one of the most severe. This univentricular defect was uniformly fatal until the introduction, 40 years ago, of a complex surgical palliation consisting of multiple staged procedures spanning the first 4 years of the child's life. While survival has improved substantially, particularly in experienced centers, ventricular failure requiring heart transplant and a number of associated morbidities remain ongoing clinical challenges for these patients. Cell-based therapies aimed at boosting ventricular performance are under clinical evaluation as a novel intervention to decrease morbidity associated with surgical palliation. In this review, we will examine the current burden of HLHS and current modalities for treatment, discuss various cells therapies as an intervention while delineating challenges and future directions for this therapy for HLHS and other congenital heart diseases.

The Fontan immunophenotype and post-transplant outcomes in children: A multi-institutional study.

Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied. In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post-HTx. The following combinations of lymphopenia and PLE were noted: +L+P, n=37; +L-P, n=23; -L+P, n=10; and -L-P, n=36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p=.9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p < .001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post-HTx, differed among the groups. Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.

108 PHEOCHROMOCYTOMA-INDUCED CARDIOGENIC SHOCK: A MULTICENTRE ANALYSIS OF CLINICAL PROFILES, MANAGEMENT AND OUTCOMES

Abstract Aims There is still uncertainty on the management of patients with pheochromocytoma-induced CS (PICS), as only a few clinical cases have been reported. The aim of this study is to investigate the clinical presentation, management, and outcome of patients with PICS. Methods We collected retrospectively 18 patients without previously known pheochromocytoma with histologically proven PICS admitted to 8 European hospitals. Results Among the 18 patients with a mean age of 50 years, 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension crises and hypotension (72%). On echocardiography, mean left ventricular ejection fraction (LVEF) was 25% with an atypical-Takotsubo pattern (basal/midventricular) in 50%. Laboratory exams showed increased inflammatory markers, in particular, the mean white blood count was 21.9*109/L. Inotropes/vasopressors were started in all patients and a temporary mechanical circulatory support (t-MCS) was required in 11 (61.1%) patients. All patients underwent surgical removal of the pheochromocytoma but 4 (22.2%) on t-MCS. Echocardiogram (16/17 patients) revealed a mean LVEF of 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. Conclusions In patients with PICS, characteristically, an atypical Takotsubo pattern was observed in almost half of the cases. Although the use of exogenous catecholamine can be perceived as deleterious, we showed a fairly good mid-term prognosis with rapid improvement of LVEF in most, even if adrenalectomy often occurred on t-MCS.

An Up-to-Date Literature Review on Ventricular Assist Devices Experience in Pediatric Hearts.

Ventricular assist devices (VAD) have gained popularity in the pediatric population during recent years, as more and more children require a heart transplant due to improved palliation methods, allowing congenital heart defect patients and children with cardiomyopathies to live longer. Eventually, these children may require heart transplantation, and ventricular assist devices provide a bridge to transplantation in these cases. The FDA has so far approved two types of device: pulsatile and continuous flow (non-pulsatile), which can be axial and centrifugal. Potential eligible studies were searched in three databases: Medline, Embase, and ScienceDirect. Our endeavor retrieved 16 eligible studies focusing on five ventricular assist devices in children. We critically reviewed ventricular assist devices approved for pediatric use in terms of implant indication, main adverse effects, and outcomes. The main adverse effects associated with these devices have been noted to be thromboembolism, infection, bleeding, and hemolysis. However, utilizing left VAD early on, before end-organ dysfunction and deterioration of heart function, may give the patient enough time to recuperate before considering a more long-term solution for ventricular support.

Abstract 13711: Cardiomyopathy Complicated by Constriction Resulting in Transplant Listing

Introduction We describe a case of severe cardiomyopathy complicated by pericardial constriction resulting from epicardial VT ablation requiring heart transplant listing. Case Presentation A 43-year-old with a history of silent MI, LV aneurysm and thrombus, cardiomyopathy (EF 15%), Stage C heart failure, and VT on amiodarone initially presented with symptomatic VT requiring AICD therapy. He underwent epicardial ablation with no immediate complications. Post-ablation, he developed polymorphic VT prompting LHC revealing new LAD artery stenosis treated with stents. He was discharged on DAPT and warfarin. He subsequently re-presented with worsening dyspnea, lethargy, and edema. Invasive hemodynamics revealed elevated filling pressures and cardiogenic shock with constrictive physiology. Milrinone and aggressive diuresis were initiated with mild improvement in symptoms. Echocardiogram and cardiac MRI confirmed diagnosis of constrictive pericarditis and presence of hemopericardium. Discussion Multidisciplinary discussions were held to determine treatment. Management of constrictive pericarditis with pericardial stripping was considered. The high-risk nature of the procedure with unknown benefit, his age, and now Stage D heart failure made sternotomy a potential increased risk for future cardiac transplant. Ultimately, decision was made for pericardiocentesis, treatment with colchicine, a switch from triple therapy to warfarin and aspirin, and listing for transplant. Surveillance RHC 6 weeks post hospitalization showed resolution of constrictive physiology and normal cardiac output on milrinone.

Abstract 15004: Characterization of Hypertrophic Cardiomyopathy Caused by Mutations in Four and a Half Lim Domains 1 Gene

Background: Mutations in Four and Half Lim domain 1 ( FHL1 ), an X-chromosome gene, have been described in rare cases of Hypertrophic Cardiomyopathy (HCM), mainly associated with myopathy. The current knowledge of the outcome of HCM caused by FHL1 mutations relies only on isolated case series. Objective: We aim to establish the prevalence of FHL1 mutations in a large population with overt HCM and clinically characterize HCM patients carrying FHL1 pathogenic and likely pathogenic genetic variants. Methods: From a total population of 794 HCM patients from 3 Referral Centers for hereditary cardiomyopathies, 349 HCM probands, who tested negative for sarcomeric mutations, were genetically screened by using Next Generation Panels including FHL1 . Moreover, all patients underwent personal and family history collection, physical examination, 12-lead electrocardiogram and echocardiography; while Cardiac Magnetic Resonance (CMR) was performed in a subgroup. Clinical and genetic data of FHL1 mutation carriers from our cohort were pooled with those of 52 FHL1 positive HCM cases from literature. Results: We identified 2 FHL1 pathogenic and 2 likely pathogenic variants (1 missense: c.764G&gt;C; 2 duplications: c.762dup and c.599dupT; and 1 deletion: c.210delG) in 6 HCM probands (0.8% of all HCM and 1.7 % of non sarcomeric HCM). As shown in Fig.1 A, pooled analysis suggested that clinical phenotype of FHL1-HCM was characterized by early-onset, severe diastolic dysfunction independently from the degree of hypertrophy and fibrosis at CMR (Fig 1 B), high sudden death risk, increased incidence of atrial fibrillation and evolution toward heart failure requiring heart transplantation, and variable skeletal muscle involvement. Conclusions: HCM patients carrying FHL1 mutations present with a worse prognosis as compared with the classic sarcomeric-HCM. A better characterization of these patients is needed for a personalized preventive and therapeutic approach.

Abstract 11117: Phase 1 Danon Disease Results: The First Single Dose Intravenous (IV) Gene Therapy (RP-A501) With Recombinant Adeno-Associated Virus (AAV9:LAMP2B) for a Monogenic Cardiomyopathy

Background: Danon disease (DD) is a rare X-linked monogenic cardiomyopathy and multisystemic disorder caused by mutations in the LAMP2 gene. Male DD patients (pts) develop severe progressive hypertrophic cardiomyopathy (HCM), left ventricular (LV) dysfunction and arrhythmias resulting in a median mortality below age 20 years (y). Methods: This open-label, single-dose, phase 1 trial enrolled male DD pts with a LAMP2 mutation and cardiomyopathy in two age groups: ≥15 y and 8-14 y. Pts received IV infusion of RP-A501, an adeno-associated virus with a normal copy of the human LAMP2B gene (AAV9:LAMP2B), at doses of 6.7 x 1013 GC/kg (low dose) and 1.1 x 1014 GC/kg (high dose). Immunomodulation (IM) included prednisone and rituximab, with additional sirolimus for the most recently treated pediatric pts. Results: Between June 2019 and March 2022, 7 males with DD age 11.7 - 21.1y (median 18.3y; N=5 adult and N=2 pediatric) received RP-A501 (N=5 low dose and N=2 high dose). 83% of pts were NYHA Class II; one was NYHA Class III. IM compliance was confirmed in 6/7 pts. All pts are alive and stable at 3-30 months (m) follow-up. One adult pt with baseline LV systolic dysfunction required heart transplant at 5m post RP-A501, most likely related to DD progression. All adverse events (AEs) related to RP-A501 or IM were manageable and reversible. No RP-A501-related SAEs were observed in the pediatric pts. On baseline endomyocardial biopsy, no pts had significant LAMP2B expression; 100% (N=6/6) of evaluable pts had cardiac LAMP2B expression within 6m of therapy with improved myocardial structure in 5/6. Pts evaluable beyond 6m had stabilized or improved BNP (N=5/5), troponin (N=5/5), and LV ejection fraction (N=5/5) by 6-12m, and stabilized/improved LV wall thickness (N=4/4) and NYHA Class (N=4/4) by 12-18m. These findings persist up to 30m post RP-A501. Conclusions: Results from this phase 1 trial in DD demonstrate that B- and T-lymphocyte directed immunomodulation enables safe IV RP-A501 gene therapy administration, resulting in cardiomyocyte transduction, LAMP2B expression, improved autophagy, and improved/stabilized serologic, echocardiographic and clinical parameters associated with survival in HCM. Updated results will be presented.

Abstract 14413: Possible Antibody Mediated Cardiac Rejection After Combined Heart-Kidney Transplant in a Sensitized Patient Associated to COVID-19 Pneumonia

Background: Antibody mediated rejection (AMR) starts with the appearance of donor-specific antibodies (DSA), followed by graft injury that may be subclinical and can progress to cardiac allograft vasculopathy (CAV) and chronic graft dysfunction. Case report A 48-year-old man with a past medical history of right nephrectomy due to congenital renal atrophy and dilated cardiomyopathy required heart transplantation at age 31, presented an episode of AMR grade 2 ten years post-transplant developing CAV with graft loss and end-stage renal disease. He was listed for a combined heart-kidney transplant. His panel reactive antibody (PRA) level was 40%, requiring desensitization therapy (plasmapheresis, intravenous gamma globulin and rituximab). At age 44, he received a heart-kidney transplant. Methylprednisolone and rabbit antithymocyte globulin were used for induction and desensitization therapy with plasmapheresis and intravenous gamma globulin at months 0-3-6-12 was continued. Maintenance immunosuppression therapy continued with tacrolimus, mycophenolic acid and prednisone. During follow-up persistent circulating DSA anti-class II HLA were detected and PRA reached 80%. He was admitted with a multifocal COVID-19 pneumonia. He had received 4 doses of the messenger RNA vaccine BNT162b2. Dexamethasone was started and mycophenolic acid was discontinued for 14 days. He did not need mechanical ventilation. Echocardiogram revealed marked concentric LVH, LVEF = 60%, grade II diastolic dysfunction and reduced global longitudinal strain (-7,6%). Pro-BNP was 962 pg/ml, and Troponin T 100 pg/ml. Endomyocardial biopsy showed no signs of cellular rejection nor capillary injury. Immunopathologic findings were negative. Coronary angiogram showed no significant lesions. AMR was suspected, the patient was treated with methylprednisolone, plasmapheresis and intravenous gamma globulin. Clinical response was satisfactory, and he was discharged in functional class I (NYHA). Conclusions Although both histological and immunopathologic studies were negative, clinical suspicion for AMR in a highly sensitized patient prevailed in the context of a recent infectious intercurrence. Other diagnosis cannot be completely ruled out in this clinical scenario.

Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain

Background The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain. Methods Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals. Results Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7–9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis (p < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain. Conclusions Glu89Lys ATTRv is a TTR variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.

S2598 Gastric Kaposi Sarcoma Presenting as Acute Upper Gastrointestinal Hemorrhage in a Heart Transplant Patient

Introduction: Kaposi sarcoma (KS), a multifocal neoplasm of lymphatic cells, occurs more often in organ transplant patients, and its pathogenesis is related to use of immunosuppressive (IS) medications. Acute gastrointestinal hemorrhage due to KS is exceedingly rare and has never been reported in a heart transplant patient. We report a case of KS presenting as gastrointestinal hemorrhage in a heart transplant patient whose bleeding resolved with supportive care and treatment of his underlying KS. Case Description/Methods: A 63-year-old man originally from Sudan with a history of non-ischemic cardiomyopathy requiring heart transplant on IS presented with melena and acute anemia. Medical history included cutaneous KS of the right leg diagnosed 1 year following transplant previously treated with paclitaxel and in clinical remission. He was treated with intravenous proton-pump inhibitor and blood transfusions. EGD showed a patch of nodular mucosa on the lesser curvature of the stomach. Pathology of the nodule showed dilated capillaries with spindle cells in the lamina propria, and staining for human herpesvirus-8 (HHV-8) was positive in the spindled cells, supporting a diagnosis of recurrent KS. He had no further bleeding, hemoglobin stabilized, and he was discharged. He was resumed on paclitaxel for recurrent KS after discharge and had no further bleeding (Figure 1). Discussion: We report a case of KS presenting with GI bleeding in a patient on chronic IS following heart transplant. While GI bleeding from KS has been reported in renal transplant recipients, this is the first such report we are aware of in a heart transplant patient. The GI tract is a common site of visceral involvement in KS, and presentation can include vomiting, diarrhea, and occult blood loss. Overt GI bleeding in KS is rare. Endoscopic appearance varies from flat lesions to polypoid or nodular growths, and histopathology shows spindle cells positive for HHV-8. Management of GI bleeding in KS depends on severity, and in less severe cases, the role of endoscopy is to confirm the visceral spread of KS with biopsy. Thereafter, management includes IS reduction and chemotherapy for refractory disease. Though KS is a rare cause of overt GI bleeding, it should be considered in patients with immunodeficiency or on chronic IS, and biopsy for suspicious lesions should be performed to confirm diagnosis.Figure 1.: Lesser curvature gastric nodule.

Natural History of MYH7-Related Dilated Cardiomyopathy

BackgroundVariants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. ObjectivesWe sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. MethodsWe studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. ResultsAt initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. ConclusionsMYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.

Mindfulness-based retreat for mothers of paediatric heart transplant recipients: protocol for a pilot intervention study

IntroductionMothers are often the primary caregivers for children requiring heart transplantation. Given that a mother’s ability to successfully cope with the demands of her caregiving role may be predictive of...

Clinical Outcomes and Effectiveness of Heart Transplantation in Patients With Systemic Light-chain Cardiac Amyloidosis.

In systemic light-chain (AL) amyloidosis, cardiac involvement is a major determinant of survival; however, cardiac response is limited even after systemic treatment in a majority of patients, and some require heart transplantation. Additionally, limited information is available on specific indications for heart transplantation. We aimed to explore clinical outcomes of cardiac amyloidosis and its association with heart transplantation, including identifying factors favoring heart transplantation amenability. We retrospectively analyzed data from patients diagnosed with AL amyloidosis with cardiac involvement between January 2007 and December 2020 at a tertiary referral center. Among 73 patients, 72 (99%) received systemic treatment, and 12 (16%) underwent heart transplantation. Characteristics at diagnosis were similar between heart transplant recipients and nonrecipients, although left ventricular ejection fraction tended to be lower in recipients (median 48% versus 57%, P = 0.085). Eight weeks after systemic treatment, 67% and 12% of patients achieved hematologic and brain natriuretic peptide responses. Overall survival was longer among heart transplantation recipients than nonrecipients, with 5-y survival rates of 61.1% (95% confidence interval, 25.5%-83.8%) versus 32.0% (95% confidence interval, 20.3%-44.4%; P = 0.022), respectively. Among the 34 with identifiable causes of death out of 51 deaths, 21 nonrecipients (62%) died of cardiac problems compared with none in the heart transplant recipients. Additionally, survival outcomes favored heart transplant recipients in most subgroups, including patients with higher Mayo 2004 European stage at diagnosis and with extracardiac involvement of amyloidosis. Heart transplantation can achieve long-term survival in appropriately selected patients with AL cardiac amyloidosis.

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p=.24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p=.33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p=.02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p=.02). HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure1. Central Illustration). [Figure: see text].

Contemporary Diagnosis and Management of Hypertrophic Cardiomyopathy: The Role of Echocardiography and Multimodality Imaging.

Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease with an estimated prevalence of 0.2–0.5%. Although the prognosis of HCM is relatively good, with an annual general mortality of ~0.7%, some patients have an increased risk of sudden death, or of developing severe heart failure requiring heart transplantation or left ventricular (LV) assist device therapy. Therefore, earlier diagnosis and proper identification of high-risk patients may reduce disease-related morbidity/mortality by promoting timely treatment. Echocardiography is the primary imaging modality for patients with suspected HCM; it plays central roles in differential diagnosis from other causes of LV hypertrophy and in evaluating morphology, hemodynamic disturbances, LV function, and associated valvular disease. Echocardiography is also an essential tool for the continuous clinical management of patients with confirmed HCM. Other imaging modalities, such as cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI), can supplement echocardiography in identifying high-risk as well as milder HCM phenotypes. The role of such multimodality imaging has been steadily expanding along with recent advancements in surgical techniques and minimally invasive procedures, and the emergence of novel pharmacotherapies directly targeting pathogenic molecules such as myosin inhibitors. Here we review essential knowledge surrounding HCM with a specific focus on structural and functional abnormalities assessed by imaging modalities, leading to treatment strategies.

Impact of donor-to-recipient weight ratio on the hospital outcomes of pediatric heart transplantation

BackgroundIdentifying the factors that can influence the prognosis and final outcomes of pediatric heart transplantation is important and makes it possible to prevent complications and improve outcomes. Coordination of donor characteristics with the recipient in terms of sex, weight, body mass index (BMI), and body surface area (BSA) is an important factor that can influence the outcome of the transplantation. There is still no consensus regarding the role of discrepancy in anthropometrics between donors and recipients. The aim of this study was to investigate the relationship between donor and recipient weight mismatch on the early outcomes of pediatric heart transplantation. In this historical cohort study, 80 children who had underwent heart transplantation for the first time between 2014 and 2019 in Shahid Rajaie Cardiovascular Medical and Research Center in Tehran, Iran, were enrolled and divided into three groups according to donor-to-recipient weight ratio (0.8 < D/RW ≤ 1.5, 1.5 < D/RW ≤ 2.5, and 2.5 < D/RW). The early outcomes of transplantation, during the first post-transplant month, including right heart failure, renal failure, graft rejection, inotrope dependency, duration of intubation, length of ICU stay, death and requiring extracorporeal membrane oxygenation, were recorded through reviewing patient records.ResultsMedian donor-to-recipient BSA ratio was directly associated with higher vasoactive–inotropic score (P = 0.038), while no significant association was found between donor-to-recipient weight ratio and vasoactive–inotropic score (P = 0.07). No significant relationship was found between other outcomes and donor-to-recipient weight ratio or donor-to-recipient BSA ratio.ConclusionsPatients who require heart transplantation may also benefit from mismatch donors, especially in those with significant cardiomegaly.

Endomyocardial biopsy-confirmed myocarditis and inflammatory cardiomyopathy: clinical profile and prognosis

Introduction and objectivesEndomyocardial biopsy (EMB) is the only technique able to establish an etiological diagnosis of myocarditis or inflammatory cardiomyopathy (ICM). The aim of this study was to analyze the clinical profile, outcomes, and prognostic factors of patients with suspected myocarditis/ICM undergoing EMB. MethodsWe retrospectively analyzed the clinical characteristics, histological findings, and follow-up data of all patients with suspected myocarditis or ICM who underwent EMB between 1997 and 2019 in a Spanish tertiary hospital. The diagnostic yield was compared using the Dallas criteria vs immunohistochemical criteria (IHC). ResultsA total of 99 patients underwent EMB (67% male; mean age, 42±15 years; mean left ventricular ejection fraction [LVEF], 34%±14%). Myocarditis or ICM was confirmed in 28% with application of the Dallas criteria and in 54% with the IHC criteria (P <.01). Lymphocytic myocarditis was diagnosed in 47 patients, eosinophilic myocarditis in 6, sarcoidosis in 3, and giant cell myocarditis in 1 patient. After a median follow-up of 18 months, 23 patients (23%) required heart transplant (HTx), a left ventricular assist device (LVAD), and/or died. Among the patients with IHC-confirmed myocarditis, 21% required HTx/LVAD or died vs 7% of those without inflammation (P=.056). The factors associated with a worse prognosis were baseline LVEF ≤ 30%, left ventricular end-diastolic diameter ≥ 60mm, and NYHA III-IV, especially in the presence of inflammation. ConclusionsEMB allows an etiological diagnosis in more than half of patients with suspected myocarditis/ICM when IHC techniques are used. IHC-confirmed inflammation adds prognostic value and helps to identify patients with a higher probability of developing complications.

Genetic Insights into Primary Restrictive Cardiomyopathy.

Restrictive cardiomyopathy is a rare cardiac disease causing severe diastolic dysfunction, ventricular stiffness and dilated atria. In consequence, it induces heart failure often with preserved ejection fraction and is associated with a high mortality. Since it is a poor clinical prognosis, patients with restrictive cardiomyopathy frequently require heart transplantation. Genetic as well as non-genetic factors contribute to restrictive cardiomyopathy and a significant portion of cases are of unknown etiology. However, the genetic forms of restrictive cardiomyopathy and the involved molecular pathomechanisms are only partially understood. In this review, we summarize the current knowledge about primary genetic restrictive cardiomyopathy and describe its genetic landscape, which might be of interest for geneticists as well as for cardiologists.

Successful Heart Transplantation in a Patient with Neonatal Marfan Syndrome

<h3>Introduction</h3> Neonatal Marfan syndrome (NMS) is a rare subtype of Marfan syndrome associated with more pronounced clinical characteristics. Patients with NMS often have more severe cardiac involvement, including atrioventricular valve prolapse and insufficiency and aortic root pathology. The development of a concurrent myopathy syndrome has not been described. We describe a case of a teenage girl with NMS who developed inotrope-dependent heart failure secondary to dilated cardiomyopathy requiring heart transplantation. <h3>Case Report</h3> The patient is a 16-year-old female with NMS, mitral valve prolapse and regurgitation, and aortopathy who underwent mitral valvuloplasty and valve-sparing aortic root replacement 5 years prior to presentation. Since that time, she had asymptomatic, progressively declining left ventricular systolic ejection fraction without progressive aortic valve or mitral disease. Her left ventricular ejection fraction was 20-25% at its nadir. Additionally, she had severe kyphosis requiring surgery three months prior to presentation and was dependent on GJ feeds for weight management. She presented in winter of 2020 with new onset heart failure requiring admission for milrinone which was unable to be weaned off due to a low cardiac output state and was listed for heart transplant on day 13 of admission. An acceptable heart became available, and she was transplanted on day 17 of admission. Her post-operative course was relatively uncomplicated. She developed ectopic atrial tachycardia, which is well-controlled with atenolol and propafenone. Whole exome sequencing confirmed that she is heterozygous for a ∼13.8 KB deletion within the <i>FBN1</i> gene, confirming her NMS diagnosis, as well as an additional novel deletion of exons 18 to 28 within <i>FBN1.</i> She has had no rejection and marked improvement in her quality of life evident by weaning off tube feedings, exercising regularly with long distance walking and attending senior year of high school. <h3>Summary</h3> The cardiac involvement in NMS and typical Marfan syndrome has generally been described as valve prolapse and aortopathy, although cardiomyopathy in the latter has been reported. Our teenage patient with NMS developed progressive LV systolic heart failure ultimately requiring a heart transplant. We believe patients with NMS that develop end-stage heart failure without treatment options should be considered for heart transplantation.