Antonio Amodeo
Professor of Cardiothoracic Surgery (Pediatric Cardiac Surgery)
Clinical Focus
- Cardiothoracic Surgery
Professional Education
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Board Certification: Ordine dei Medici Chirurghi e degli Odontoiatri della provincial di Pavia, Cardiothoracic Surgery (1991)
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Fellowship: Bambino Gesu Paediatric Hospital of Rome (1990) Italy
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Residency: Naples University Medical School at Universitaria Federico II (1983) Italy
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Medical Education: Naples University Medical School at Universitaria Federico II (1983) Italy
Contact
Additional Clinical Info
https://orcid.org/0000-0003-1051-3267All Publications
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Heart Transplantation and Ventricular Assist Device in Duchenne Muscular Dystrophy: A New Era.
Pediatric transplantation
2026; 30 (1): e70253
Abstract
Duchenne muscular dystrophy (DMD) is an X-linked genetic neuromuscular disorder that is caused by a mutation in the dystrophin gene. The disease is characterized by progressive weakness of skeletal muscle, resulting in loss of ambulation and eventually respiratory insufficiency. Cardiac muscle is also involved, and cardiomyopathy is a prominent feature of DMD. The care of patients with DMD has changed in important ways over the past 15 years, with the use of chronic steroid therapy combined with noninvasive respiratory support such as continuous positive airway pressure for home use. More recently, therapies targeting specific genetic mutations in DMD have been approved, using gene-skipping oligonucleotides, and many other novel therapies are being evaluated in clinical trials, including mini-dystrophin genes delivered by viral vectors. In view of this new era in care and outcomes, it is appropriate to review the role of advanced cardiac therapies such as ventricular assist devices and heart transplantation in the care of this population. In September 2024, a group of healthcare professionals with expertise in DMD and heart failure convened to review this topic; the consensus opinion of this group (DMD Cardiac Care Consortium) is presented in this manuscript.
View details for DOI 10.1111/petr.70253
View details for PubMedID 41424087
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Long-term incidence of arrhythmias in extracardiac conduit Fontan and comparison between systemic left and right ventricle
EUROPACE
2024; 26 (5)
Abstract
The extracardiac conduit-Fontan (ECC) has become the preferred technique for univentricular heart palliation, but there are currently no data on the incidence of long-term arrhythmias. This study investigated the incidence of arrhythmias and relation to single ventricle morphology in the long-term follow-up (FU) in ECC.All patients with ECC performed in our Centre between 1987 and 2017 were included (minimum FU 5 years). Of 353 consecutive patients, 303 [57.8% males, aging 8-50 (median 20) years at last FU] were considered and divided into two groups depending on left (194 in Group 1) or right (109 in Group 2) ventricular morphology. Eighty-five (28%) experienced ≥1 arrhythmic complications, with early and late arrhythmias in 17 (5.6%) and 73 (24.1%) patients, respectively. Notably, late bradyarrhythmias occurred after 6 years in 21 (11%) patients in Group 1, and in 15 (13.8%) in Group 2 [P = 0.48]. Late tachyarrhythmias occurred in 55 (18.2%) patients after 12 years: 33 (17%) in Group 1 and 22 (20.2%) patients in Group 2 [P = 0.5]. Ventricular tachycardias (VT) were documented after 12.5 years in 14 (7.2%) patients of Group 1 and 15 (13.8%) of Group 2 [P = 0.06] with a higher incidence in Group 2 during the FU [P = 0.005].Extracardiac conduit is related to a significant arrhythmic risk in the long-term FU, higher than previously reported. Bradyarrhythmias occur earlier but are less frequent than tachyarrhythmias. Interestingly, patients with systemic right ventricle have a significantly higher incidence of VT, especially in a very long FU.
View details for DOI 10.1093/europace/euae097
View details for Web of Science ID 001220161900003
View details for PubMedID 38650062
View details for PubMedCentralID PMC11089577
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Durable left ventricular assist device explantation following recovery in paediatric patients: Determinants and outcome after explantation
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2024; 65 (4)
Abstract
Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited.All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models.The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093-0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545-8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%).Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.
View details for DOI 10.1093/ejcts/ezae126
View details for Web of Science ID 001203437800001
View details for PubMedID 38613845
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Changes in adiponectin system after ventricular assist device in pediatric heart failure.
JHLT open
2024; 3: None
Abstract
Background: Ventricular assist device (VAD) implant represents a therapeutic option for pediatric patients with end-stage heart failure (HF). Heart unloading by VAD can modify several molecular pathways underlying cardiac function in HF. Among them, the potential role of microRNA (miRNAs) in response to VAD implant is emerging. This study was aimed at investigating in HF pediatric patients the effect of VAD-modified miRNAs on the adiponectin (ADPN) system, known to exert cardioprotective actions.Methods: ADPN was measured in plasma samples obtained from HF children, before and 1month after VAD implant, and from healthy control children. miRNA profile and molecules belonging to ADPN system were determined in cardiac biopsies collected at the time of VAD implantation (pre-VAD) and at the moment of heart transplant (post-VAD). An in vitro study using HL-1 cell line was performed to verify the regulatory role of the VAD-modified miRNA on the ADPN system.Results: VAD implant did not affect circulating and cardiac levels of ADPN, but increased the cardiac mRNA expression of ADPN receptors, including AdipoR1, AdipoR2, and T-cad. AdipoR2 and T-cad were inversely related to the VAD-modified miRNA levels. The in vitro study confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2, and of miR-199b-5p on T-cad.Conclusions: These data suggest that VAD treatment could regulate the expression of the cardioprotective ADPN system by epigenetic mediators, suggesting that miRNAs have a potential role as therapeutic targets to improve cardiac function in HF pediatric patients.
View details for DOI 10.1016/j.jhlto.2023.100041
View details for PubMedID 38357297
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Case report: Coronary allograft vasculopathy: an accurate reflection of the histopathological findings on cardiovascular magnetic resonance imaging
FRONTIERS IN CARDIOVASCULAR MEDICINE
2023; 10: 1123212
Abstract
Heart transplant recipients undergo extensive invasive and non-invasive postoperative screening to exclude complications, such as allograft rejection and vasculopathy. Cardiac magnetic resonance imaging is a non-invasive, non-irradiating, diagnostic tool for monitoring graft health and identifying possible tissue rejection or myocardial fibrosis. We describe the case of a 29-year-old female heart transplant recipient admitted to our care center with a worsening clinical condition. The patient underwent clinical evaluation, blood tests, including troponin I and N-terminal pro brain type natriuretic peptide, transthoracic echocardiography, invasive coronary angiography, and cardiovascular magnetic resonance imaging. Cardiovascular magnetic resonance imaging showed widespread sub-epicardial hyperintensity of the myocardial segments along the course of the coronary arteries. T2 mapping sequences showed an elevated value and the myocardial native T1 values and extracellular volume percentage were significantly increased. Late gadolinium enhancement demonstrated a diffuse sub-epicardial hypersignal along the lateral, free, and left ventricular walls. All the sequences evidenced widespread hyper-enhancement of epicardial fat along the course of the thickened main coronary artery walls. One month later, the recipient underwent re-transplantation due to progressive worsening of the clinical condition and refractoriness to intravenous medication. The anatomopathological findings of the explanted heart provided impressive visualization of structural and histopathological changes. These results could guide the tailoring of preventive therapeutic strategies and non-invasive monitoring of cardiac grafts.
View details for DOI 10.3389/fcvm.2023.1123212
View details for Web of Science ID 000997225800001
View details for PubMedID 37265562
View details for PubMedCentralID PMC10229782
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Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement
LANCET RESPIRATORY MEDICINE
2023; 11 (5): 477-492
Abstract
Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.
View details for DOI 10.1016/S2213-2600(22)00535-5
View details for Web of Science ID 000996781200001
View details for PubMedID 36924784
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Parvovirus B19 Myocarditis in a Covid19 MIS-C Syndrome: Cause or Causality?
ELSEVIER SCIENCE INC. 2023: S259-S260
View details for Web of Science ID 000992480600569
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lCombined Strategy to Induce Myocardial Recovery in Children with Advanced Heart Failure: Single Center Retrospective Study
ELSEVIER SCIENCE INC. 2023: S106-S107
View details for Web of Science ID 000992480600212
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Endomyocardial Biopsy in Myocarditis Identifies Factors That Predict Outcome in Children
ELSEVIER SCIENCE INC. 2023: S152
View details for Web of Science ID 000992480600315
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Use of implantable cardioverter-defibrillator in children supported with ventricular assist device: An analysis of data from teh EUROMACS registry
ARTIFICIAL ORGANS
2023; 47 (8): 1319-1325
Abstract
Data on the use and outcome of children on ventricular assist device (VAD) support provided with an implantable cardioverter-defibrillator (ICD) remains poor.A retrospective analysis of the EUROMACS database on children supported with VAD < 19 years of age from January 1, 2009 to April 1, 2020. Patients with missing data on status of ICD, missing baseline and/or follow up information were excluded. The primary independent variable of interest was the concomitant presence or absence of an ICD at the time of VAD placement. Kaplan-Meier survival analysis was performed to evaluate survival differences between children on VAD with and without an ICD.Out of 303 patients provided with a VAD, 7% (7♀, 15♂) had an ICD implanted and formed the study group. Median age was 14 years, median weight was 43.5 kg, and median BSA was 1.39. Median Intermacs stage was 2 (range: 1-7). Seventeen patients (77%) were transplanted, 4 (18%) died while on support, and 1 (5%) was weaned from device after myocardial recovery. Median time on support was 68 days compared to 361 days in the control group (p: 0.01). Three patients underwent device exchange due to thrombus formation in the pump. There was no difference in survival between groups (p = 0.342).The presence of ICD in pediatric patients supported with a VAD is low (7%). Children on VAD support provided with an ICD do not have a survival benefit compared to children without an ICD.
View details for DOI 10.1111/aor.14515
View details for Web of Science ID 000958715900001
View details for PubMedID 36855905
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Remember Friedreich ataxia even in a toddler with apparently isolated dilated (not hypertrophic!) cardiomyopathy. Revisited
MINERVA PEDIATRICS
2023; 75 (1): 117-123
Abstract
Friedreich ataxia (FRDA) is the most common form of ataxia in late childhood. Neurological manifestations often precede cardiac involvement, presenting mainly as hypertrophic cardiomyopathy. We describe a toddler with apparently isolated severe heart failure, successfully managed with heart transplant (HT). Although well described in adolescents and adults, onset of FRDA is very uncommon in toddlers and neurological ataxic features are predominant. The presenting symptom of cardiomyopathy is very rare. Similar history is rarely reported in literature, that we described, including an aggressive cardiomyopathy in children younger than 5 years-old. RESULTS: Our patient was diagnosed with FRDA at a postoperative stage due to minimal neurological manifestations. Moreover, the novelty of this study lies in demonstrating a major DNA triplet repeat expansion in skeletal muscle compared to DNA from peripheral blood leukocytes. These results support the concept that triplet repeat expansion is variable among different tissues in FRDA, and in our case it was more expanded in the post mitotic muscular tissue than in blood cells. We believe on the importance of taking in consideration this rare condition even in a toddler with apparently isolated cardiomyopathy and especially when conventional investigations give negative results. We discuss potential trigger effect of HT as a precipitating factor in manifesting neurological symptoms. This observation corresponds to our experience and relates to three patients described so far (the third patient died suddenly). Early onset cardiomyopathy with FRDA should increase awareness of this rare condition and we highlight HT successful outcome. Further reports are needed to delineate this rare condition in youngsters.
View details for DOI 10.23736/S2724-5276.21.05969-3
View details for Web of Science ID 000960528900014
View details for PubMedID 33820410
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Outcomes in small children on Berlin Heart EXCOR support: age and body surface area as clinical predictive factors
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2022; 63 (1)
Abstract
The Berlin Heart EXCOR (BHE) offers circulatory support across all paediatric ages. Clinically, the necessary care and the outcomes differ in various age groups. The EUROMACS database was used to study age- and size-related outcomes for this specific device.All patients <19 years of age from the EUROMACS database supported with a BHE between 2000 and November 2021 were included. Maximally selected rank statistics were used to determine body surface area (BSA) cut-off values. Multivariable Cox proportional hazard regression using ridge penalization was performed to identify factors associated with outcomes.In total, 303 patients were included [mean age: 2.0 years (interquartile range: 0.6-8.0, males: 48.5%)]. Age and BSA were not significantly associated with mortality (n = 74, P = 0.684, P = 0.679). Factors associated with a transplant (n = 175) were age (hazard ratio 1.07, P = 0.006) and aetiology other than congenital heart disease (hazard ratio 1.46, P = 0.020). Recovery rates (n = 42) were highest in patients with a BSA of <0.53 m2 (21.8% vs 4.3-7.6% at 1 year, P = 0.00534). Patients with a BSA of ≥0.73 m2 had a lower risk of early pump thrombosis but a higher risk of early bleeding compared to children with a BSA of <0.73 m2.Mortality rates in Berlin Heart-supported patients cannot be predicted by age or BSA. Recovery rates are remarkably high in the smallest patient category (BSA <0.53 m2). This underscores that the BHE is a viable therapeutic option, even for the smallest and youngest patients.
View details for DOI 10.1093/ejcts/ezac516
View details for Web of Science ID 000910891400007
View details for PubMedID 36346169
View details for PubMedCentralID PMC9825200
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Jacobsen Syndrome with Hypoplastic Left Heart Syndrome: Outcome after Cardiac Transplantation
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
2023; 10 (1)
Abstract
Jacobsen syndrome (JS) is a rare syndrome caused by a deletion of chromosome 11q. We report a patient with JS and hypoplastic left heart syndrome (HLHS) who required cardiac transplantation. She had many of the recognized morphological features in addition to immunological (lymphopenia) and hematological (thrombocytopenia) issues. The patient underwent a Norwood procedure with a modified Blalock-Taussig shunt (MBTS) and subsequently a Glenn procedure at six months of age. She developed desaturation, with severe tricuspid regurgitation and right ventricular dysfunction, and underwent heart transplantation at 7 months of age. After the transplant, she was hospitalized several times for severe infections. The diagnosis of Jacobsen syndrome came 2 months after transplant. Now, 5 years post-transplant, she is in relatively good health-her heart is functioning normally, her hospitalization rate is getting lower, and her immunological profile is stable.
View details for DOI 10.3390/jcdd10010008
View details for Web of Science ID 000915126900001
View details for PubMedID 36661903
View details for PubMedCentralID PMC9864704
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Heart rate reduction as a marker to optimize carvedilol treatment and enhance myocardial recovery in pediatric dilated cardiomyopathy
FRONTIERS IN PHYSIOLOGY
2022; 13: 1001752
Abstract
Introduction: An elevated heart rate is associated with an increased risk of death or cardiac transplant in children with dilated cardiomyopathy (DCM). Whether heart rate is a clinical marker to address therapy, is poorly investigated in children. Aim: To investigate the relationship between heart rate reduction (HRR) and left ventricular ejection fraction (LVEF) in DCM, treated with carvedilol. Methods: This is a multi center retrospective analysis conducted on all children with DCM (aged <18 years) between 2013 and 2020, with LVEF <40% and treated with carvedilol. Carvedilol was up titrated to the maximal tolerated dose or to 1 mg/kg/day. Echocardiographic data on left ventricular function and dimension were collected. The relationship between HRR and LVEF, left ventricular end-diastolic (LVEDd) and end-systolic diameter (LVESd) was assessed before and after HRR with carvedilol, using regression analysis. Results: 100 patients were enrolled (M: 51%; age 7 ± 8 years). The mean LVEF was 30.2 ± 10% before treatment and 43.7 ± 9.6% after treatment, at the maximum therapeutic dose (p < 0.0001). There was a positive relationship between HRR and increase in LVEF (R 2 = 0.06, p = 0.014). A HRR of >20% correlated with an improvement in LVEF >13%. At 3 years follow up, HRR demonstrated a significant reduction of LVESd (R2 = 0.1, p = 0.003) LVEDd (R2 = 0.07, p = 0.008) and LVEF recovery up to 15% (p < 0.0001). No deaths or heart transplant occurred during follow-up. Conclusion: This study demonstrates that HRR is safe and improvement in LVEF is related to the degree of HRR. The magnitude of LVEF improvement was enhanced by a major reduction in HR. It provides evidence that HRR could be used as a clinical marker to treat HF in children.
View details for DOI 10.3389/fphys.2022.1001752
View details for Web of Science ID 000899707500001
View details for PubMedID 36531178
View details for PubMedCentralID PMC9757159
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Impact of severe valvular heart disease in adult congenital heart disease patients
FRONTIERS IN CARDIOVASCULAR MEDICINE
2022; 9: 983308
Abstract
The clinical impact of valvular heart disease (VHD) in adult congenital heart disease (ACHD) patients is unascertained. Aim of our study was to assess the prevalence and clinical impact of severe VHD (S-VHD) in a real-world contemporary cohort of ACHD patients.Consecutive patients followed-up at our ACHD Outpatient Clinic from September 2014 to February 2021 were enrolled. Clinical characteristics and echocardiographic data were prospectively entered into a digitalized medical records database. VHD at the first evaluation was assessed and graded according to VHD guidelines. Clinical data at follow-up were collected. The study endpoint was the occurrence of cardiac mortality and/or unplanned cardiac hospitalization during follow-up.A total of 390 patients (median age 34 years, 49% males) were included and S-VHD was present in 101 (25.9%) patients. Over a median follow-up time of 26 months (IQR: 12-48), the study composite endpoint occurred in 76 patients (19.5%). The cumulative endpoint-free survival was significantly lower in patients with S-VHD vs. patients with non-severe VHD (Log rank p < 0.001). At multivariable analysis, age and atrial fibrillation at first visit (p = 0.029 and p = 0.006 respectively), lower %Sat O2, higher NYHA class (p = 0.005 for both), lower LVEF (p = 0.008), and S-VHD (p = 0.015) were independently associated to the study endpoint. The likelihood ratio test demonstrated that S-VHD added significant prognostic value (p = 0.017) to a multivariate model including age, severe CHD, atrial fibrillation, %Sat O2, NYHA, LVEF, and right ventricle systolic pressure > 45 mmHg.In ACHD patients, the presence of S-VHD is independently associated with the occurrence of cardiovascular mortality and hospitalization. The prognostic value of S-VHD is incremental above other established prognostic markers.
View details for DOI 10.3389/fcvm.2022.983308
View details for Web of Science ID 000897788100001
View details for PubMedID 36523370
View details for PubMedCentralID PMC9744774
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Cardiovascular Involvement in Pediatric <i>FLNC</i> Variants: A Case Series of Fourteen Patients
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
2022; 9 (10)
Abstract
Filamin C is a protein specifically expressed in myocytes and cardiomyocytes and is involved in several biological functions, including sarcomere contractile activity, signaling, cellular adhesion, and repair. FLNC variants are associated with different disorders ranging from striated muscle (myofibrillar distal or proximal) myopathy to cardiomyopathies (CMPs) (restrictive, hypertrophic, and dilated), or both. The outcome depends on functional consequences of the detected variants, which result either in FLNC haploinsufficiency or in an aberrant protein, the latter affecting sarcomere structure leading to protein aggregates. Cardiac manifestations of filaminopathies are most often described as adult onset CMPs and limited reports are available in children or on other cardiac spectrums (congenital heart defects-CHDs, or arrhythmias). Here we report on 13 variants in 14 children (2.8%) out of 500 pediatric patients with early-onset different cardiac features ranging from CMP to arrhythmias and CHDs. In one patient, we identified a deletion encompassing FLNC detected by microarray, which was overlooked by next generation sequencing. We established a potential genotype-phenotype correlation of the p.Ala1186Val variant in severe and early-onset restrictive cardiomyopathy (RCM) associated with a limb-girdle defect (two new patients in addition to the five reported in the literature). Moreover, in three patients (21%), we identified a relatively frequent finding of long QT syndrome (LQTS) associated with RCM (n = 2) and a hypertrabeculated left ventricle (n = 1). RCM and LQTS in children might represent a specific red flag for FLNC variants. Further studies are warranted in pediatric cohorts to delineate potential expanding phenotypes related to FLNC.
View details for DOI 10.3390/jcdd9100332
View details for Web of Science ID 000874377100001
View details for PubMedID 36286284
View details for PubMedCentralID PMC9604120
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Cerebrovascular accidents in paediatric patients supported by the Berlin Heart EXCOR
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2022; 62 (3)
Abstract
Ventricular assist device support as a bridge to transplant or recovery is a well-established therapy in children on the cardiac transplant waiting list. The goal of this study was to investigate the incidence of and the associated factors for cerebrovascular accidents in paediatric patients supported by a Berlin Heart EXCOR.All patients <19 years of age supported by a Berlin Heart EXCOR between January 2011 and January 2021 from the European Registry for Patients with Mechanical Circulatory Support were included.In total, 230 patients were included. A total of 140 (60.9%) patients had a diagnosis of dilated cardiomyopathy. 46 patients (20.0%) sustained 55 cerebrovascular accidents, with 70.9% of the episodes within 90 days after the ventricular assist device was implanted. The event rate of cerebrovascular accidents was highest in the first era (0.75). Pump thrombosis and secondary need for a right ventricular assist device were found to be associated with a cerebrovascular accident (hazard ratio 1.998, P = 0.040; hazard ratio 11.300, P = 0.037). At the 1-year follow-up, 44.4% of the patients had received a transplant, 13.1% were weaned after recovery and 24.5% had died. Event rates for mortality showed a significantly decreasing trend.Paediatric ventricular assist device support is associated with important adverse events, especially in the early phase after the device is implanted. Pump thrombosis and the need for a secondary right ventricular assist device are associated with cerebrovascular accidents. Furthermore, an encouragingly high rate of recovery in this patient population was shown, and death rates declined. More complete input of data into the registry, especially concerning anticoagulation protocols, would improve the data.
View details for DOI 10.1093/ejcts/ezac381
View details for Web of Science ID 000843704400004
View details for PubMedID 35849328
View details for PubMedCentralID PMC9789740
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The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): third Paediatric (Paedi-EUROMACS) report
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2022; 62 (2)
Abstract
A third paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight.Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (<19 years of age) performed from 1 January 2000 to 31 December 2020 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding.Twenty-five hospitals contributed 537 registered implants in 480 patients. The most frequent aetiology of heart failure was any form of cardiomyopathy (59%), followed by congenital heart disease and myocarditis (15% and 14%, respectively). Competing outcomes analysis revealed that a total of 86% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 21.9% died while on support. At 12 months, 45.1% received transplants, 7.5% were weaned from their device and 20.8% died. The 3-month adverse events rate was 1.59 per patient-year for device malfunction including pump exchange, 0.7 for major bleeding, 0.78 for major infection and 0.71 for neurological events.The overall survival rate was 79.2% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age; P = 0.01) and lower weight (<20 kg; P = 0.015). Transplant rates at 6 months continue to be low (33.2%).
View details for DOI 10.1093/ejcts/ezac355
View details for Web of Science ID 000822875300003
View details for PubMedID 35758622
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Late outcome of extracardiac Fontan patients: 32 years of follow-up
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2022; 62 (1)
Abstract
We sought to evaluate the long-term survival and risk factors for morbidity and mortality in our cohort of patients after extracardiac (EC) Fontan.We collected and analysed follow-up data until September 2020 for all patients who underwent EC Fontan operation at our institution from November 1988 to November 2015.Out of 406 patients treated with EC Fontan at a mean age of 5.4 ± 4.5 years, 372 (91.6%) were discharged home; 15% were lost to follow-up. The median follow-up was 14.6 years (interquartile range 8.7-20.3). Two hundred patients (54%) had a good long-term outcome, with an event-free long-term survival, but late adverse events of any kind needing interventional or surgical reoperations were reported in 128 patients (34%). Forty-four patients (12%) developed late Fontan failure. Thirty-seven survivors (10%) had late arrhythmias, with the need for pacemaker implantation. Obstruction of the cavopulmonary pathway occurred in 49 patients (13%), but just 8 patients needed conduit surgical replacement. At 32 years, the survival probability was 84%. The risk of orthotopic heart transplant, considering death as a competing event (showed as cumulative incidence), was 12.5%. A preoperative diagnosis of hypoplastic left heart syndrome was an independent risk factor for the need for heart transplant.The EC Fontan shows satisfactory long-term survival and low incidence of adverse events and late failure. Conduit replacement is rare, and its longevity may not represent a substantial issue in these patients. However, as with other technical variants, the need for reoperations during long-term follow-up is a significant challenge.
View details for DOI 10.1093/ejcts/ezac301
View details for Web of Science ID 000799476200001
View details for PubMedID 35543463
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Cardiomyopathy Due to Propionic Acidemia: Clinical Features and Therapeutic Implication
ELSEVIER SCIENCE INC. 2022: S503
View details for Web of Science ID 000780119701502
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Real-World Use of Carvedilol in Children With Dilated Cardiomyopathy: Long-Term Effect on Survival and Ventricular Function
FRONTIERS IN PEDIATRICS
2022; 10: 845406
Abstract
Carvedilol is recommended for chronic heart failure (HF) treatment in children. However, the ideal dosage and administration are not standardized, and data on its long-term effects are lacking. This study aimed to assess the effect of a high dosage regimen of carvedilol on cardiac outcomes in children with HF.We conducted a retrospective cohort study including all children with HF and dilated cardiomyopathy. We analyzed medical records before starting treatment, at 1 and 3 years after reaching the maximum therapeutic dosage. All data were compared with a historical control group. Kaplan-Meier analysis and Cox proportional hazard regression have been used to evaluate the effect of high dosage carvedilol therapy. The main outcome was a composite of all-cause mortality and heart transplant.One hundred thirty-five were included in the study and 65 treated with a high dosage of carvedilol regimen (up to 1 mg/kg/day). Heart rate reduction (mean reduction 30%, p < 0.0001) and ejection fraction improvement (32 ± 9.4 vs. 45. ± 10.1%, p < 0.0001) were statistically significant in those. Long-term survival and freedom from heart transplant were significantly improved in those treated with high dosage carvedilol therapy (p = 0.00001).Treatment with the high dosage of carvedilol, in addition to standard HF therapy, significantly improves ventricular function and survival in children with dilated cardiomyopathy and chronic HF.
View details for DOI 10.3389/fped.2022.845406
View details for Web of Science ID 000790878200001
View details for PubMedID 35433536
View details for PubMedCentralID PMC9010785
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Heart Rate and Left Ventricular Ejection Fraction in Dilated Cardiomyopathy: How Much We Have to Low?
ELSEVIER SCIENCE INC. 2022: S503
View details for Web of Science ID 000780119701501
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Right ventricle-pulmonary artery coupling in repaired tetralogy of Fallot with pulmonary regurgitation: Clinical implications
ARCHIVES OF CARDIOVASCULAR DISEASES
2022; 115 (2): 67-77
Abstract
Right ventricle-pulmonary artery (RV-PA) coupling is a strong prognostic marker in several clinical settings, but few studies have focused on its role in repaired tetralogy of Fallot (rToF) with pulmonary regurgitation.To assess whether differences exist in RV-PA coupling, estimated by echocardiography, between patients with rToF and pulmonary regurgitation with or without an indication for pulmonary valve replacement (PVR).The study population included 40 patients with rToF, who were allocated to two groups: 20 with an indication for PVR (i-PVR group); and 20 without an indication for PVR (ni-PVR group). Forty healthy controls were also included. All subjects underwent echocardiography, and cardiac magnetic resonance (CMR) was available in 27/40 patients with rToF. RV-PA coupling was assessed by echocardiographic tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) and right ventricular stroke volume/right ventricular end-systolic volume (RVSV/RVESV) by CMR.TAPSE was similar in the i-PVR and ni-PVR groups (19.0±3.4 vs 18.8±2.7mm; P=0.97) whereas RV-PA coupling was significantly worse in the i-PVR group versus the ni-PVR group (TAPSE/PASP 0.8±0.3 vs 1.1±0.5mm/mmHg; P=0.001), and in the i-PVR group versus the control group (P=0.02); there was no difference between the ni-PVR and control groups (P=0.29). CMR data confirmed the echocardiography results, with a significant difference in RV-PA coupling between the i-PVR and ni-PVR groups (RVSV/RVESV 0.9±0.2 vs 1.2±0.3mL/min/mL; P=0.01).This study demonstrates worse RV-PA coupling, despite normal RV systolic function, in patients with rToF with an indication for PVR. RV-PA coupling could be a sensitive marker of a progressive maladaptive RV response to long-standing volume overload in rToF before the onset of clinical symptoms and RV systolic dysfunction.
View details for DOI 10.1016/j.acvd.2021.12.006
View details for Web of Science ID 000758988800002
View details for PubMedID 35125276
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BNT162B2 mRNA COVID-19 Vaccine in Heart and Lung Transplanted Young Adults: Is an Alternative SARS-CoV-2 Immune Response Surveillance Needed?
TRANSPLANTATION
2022; 106 (2): E158-E160
View details for DOI 10.1097/TP.0000000000003999
View details for Web of Science ID 000748941100006
View details for PubMedID 34954734
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Arrhythmogenic cardiomyopathy in children according to "Padua criteria": Single pediatric center experience
INTERNATIONAL JOURNAL OF CARDIOLOGY
2022; 350: 83-89
Abstract
The aim of this study was to report clinical and arrhythmic features in a pediatric population affected by arrhythmogenic cardiomyopathy (ACM). Moreover, we assessed the concordance between the 2010 International Task Force criteria (ITF) and the 2020 Padua criteria.Inclusion criteria were "definite" or "borderline" ACM diagnosed according to the "Padua criteria" in patients <18 years old. History, electrocardiograms, ECG-holter monitorings, exercise testings, imaging investigations, electrophysiological studies, genetic testings and follow-up data were collected.We enrolled 21 patients (mean age 13.9 ± 2 years). Most of them presented for minor arrhythmias. Premature ventricular complexes burden was 7.9 ± 10%. Cardiac magnetic resonance (19/21, 90.5% patients) showed right ventricular (RV) dilatation, wall motion abnormalities and late gadolinium enhancement (LGE) of both ventricles as predominant features [in 9 patients (52.9%) LGE left ventricle]. Genetic results (19/21 patient) showed compound heterozygous variants in 3/19 patients (15.8%), digenic in 3/19 (15.8%) and single in 6/19 (31.6%). Cardiac defibrillator (ICD) was indicated in 15 patients (71.4%): 6 in class I, 7 in class IIa, 2 in class IIb. Appropriate shocks occurred in 2 patients (13.3%), follow-up 5.46 ± 3.17 years According to 2010 ITF criteria: among the 18 patients with a "definite" ACM diagnosis, one patient would have had a "borderline" diagnosis, three a "possible" diagnosis and one no diagnosis and among the three patients with "borderline" diagnosis two would have had a "possible" diagnosis.Pediatric ACM can be diagnosed in the majority of cases secondary to incidental finding of simple ventricular arrhythmias. PVC burden is low and exercise induced arrhythmias rarely occur. Few patients with ICD experience appropriate shocks. "Padua criteria" improve the diagnostic accuracy.
View details for DOI 10.1016/j.ijcard.2022.01.008
View details for Web of Science ID 000755777900015
View details for PubMedID 34998950
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Early Right Heart Chambers Reverse Remodeling in Patients Operated in Adulthood for Congenital Lesions Associated with Right Heart Chambers Enlargement
WORLD JOURNAL FOR PEDIATRIC AND CONGENITAL HEART SURGERY
2021; 12 (6): 747-753
Abstract
Progressive right heart chambers dilatation is frequent in the adult congenital heart disease (ACHD) population. We evaluated the immediate and mid-term response of right heart chambers to surgery performed in adulthood for lesions associated with right heart chambers enlargement.Thirty-six adult patients with lesions associated with right heart chambers enlargement submitted to surgery were studied. We collected echocardiographic data of right ventricle (RV) mid-diameter, right atrial volume indexed, RV systolic pressure, and tricuspid annular plane systolic excursion (TAPSE) prior to surgery (T0), at 2 to 5 days (T1), and 3 to 6 months (T2) after surgery.At T1, we observed a significant decrease of RV mid-diameter (47.2 ± 8.4 vs. 39.6 ± 7.4 mm, P < .001), right atrial volume indexed (45.6 ± 26.6 vs. 27.2 ± 11 ml/m2, P < .001), and RV systolic pressure (39 ± 14.8 vs. 32.8 ± 11.3 mm Hg, P = .03). At T2, a further significant deviation in the rate of RV diameter (39.6 ± 7.4 vs. 34.5 ± 5.1 mm, P < .001), in RV systolic pressure (32.8 ± 11.3 vs. 25.3 ± 5 mm Hg, P = .03) and TAPSE (13.9 ± 3.2 vs. 15.8 ± 2.6 mm, P < .001) was observed.Positive right heart chambers remodeling occurs as early as in the immediate post-operative period in most ACHD patients operated for lesions associated with right heart chambers enlargement.
View details for DOI 10.1177/21501351211040474
View details for Web of Science ID 000725028500010
View details for PubMedID 34846962
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Epigenetic Regulation of Cardiac Troponin Genes in Pediatric Patients with Heart Failure Supported by Ventricular Assist Device
BIOMEDICINES
2021; 9 (10)
Abstract
Ventricular Assist Device (VAD) therapy is considered as a part of standard care for end-stage Heart Failure (HF) children unresponsive to medical management, but the potential role of miRNAs in response to VAD therapy on molecular pathways underlying LV remodeling and cardiac function in HF is unknown. The aims of this study were to evaluate the effects of VAD on miRNA expression profile in cardiac tissue obtained from HF children, to determine the putative miRNA targets by an in-silico analysis as well as to verify the changes of predicated miRNA target in the same cardiac samples. The regulatory role of selected miRNAs on predicted targets was evaluated by a dedicated in vitro study. miRNA profile was determined in cardiac samples obtained from 13 HF children [median: 29 months; 19 LVEF%; 9 Kg] by NGS before VAD implant (pre-VAD) and at the moment of heart transplant (Post-VAD). Only hsa-miR-199b-5p, hsa-miR-19a-3p, hsa-miR-1246 were differentially expressed at post-VAD when compared to pre-VAD, and validated by real-time PCR. Putative targets of the selected miRNAs were involved in regulation of sarcomere genes, such as cardiac troponin (cTns) complex. The expression levels of fetal ad adult isoforms of cTns resulted significantly higher after VAD in cardiac tissue of HF pediatric patients when compared with HF adults. An in vitro study confirmed a down-regulatory effect of hsa-miR-19a-3p on cTnC expression. The effect of VAD on sarcomere organization through cTn isoform expression may be epigenetically regulated, suggesting for miRNAs a potential role as therapeutic targets to improve heart function in HF pediatric patients.
View details for DOI 10.3390/biomedicines9101409
View details for Web of Science ID 000715518600001
View details for PubMedID 34680526
View details for PubMedCentralID PMC8533380
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Dynamic superior vena cava occlusion with an atrial implanted pediatric right ventricular assist device
JTCVS TECHNIQUES
2021; 9: 137-140
View details for DOI 10.1016/j.xjtc.2021.05.022
View details for Web of Science ID 000706410900043
View details for PubMedID 34647083
View details for PubMedCentralID PMC8501130
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Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R)
ESC HEART FAILURE
2021; 8 (6): 5542-5550
Abstract
Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF.The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment.The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.
View details for DOI 10.1002/ehf2.13574
View details for Web of Science ID 000695059000001
View details for PubMedID 34510806
View details for PubMedCentralID PMC8712832
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The frequency of rare and monogenic diseases in pediatric organ transplant recipients in Italy
ORPHANET JOURNAL OF RARE DISEASES
2021; 16 (1): 374
Abstract
Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients' quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort.To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002-2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants.This work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.
View details for DOI 10.1186/s13023-021-02013-x
View details for Web of Science ID 000693048400002
View details for PubMedID 34481500
View details for PubMedCentralID PMC8418291
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Pediatric Mechanical Circulatory Support: Pathophysiology of Pediatric Hemostasis and Available Options
FRONTIERS IN CARDIOVASCULAR MEDICINE
2021; 8: 671241
Abstract
Pediatric mechanical circulatory support (MCS) is considered a strategy for heart failure management as a bridge to recovery and transplantation or as a destination therapy. The final outcome is significantly impacted by the number of complications that may occur during MCS. Children on ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are at high risk for bleeding and thrombotic complications that are managed through anticoagulation. The first detailed guideline in pediatric VADs (Edmonton Anticoagulation and Platelet Inhibition Protocol) was based on conventional antithrombotic drugs, such as unfractionated heparin (UFH) and warfarin. UFH is the first-line anticoagulant in pediatric MCS, although its profile is not considered optimal in pediatric setting. The broad variation in heparin doses among children is associated with frequent occurrence of cerebrovascular accidents, bleeding, and thrombocytopenia. Direct thrombin inhibitors (DTIs) have been utilized as alternative strategies to heparin. Since 2018, bivalirudin has become the chosen anticoagulant in the long-term therapy of patients undergoing MCS implantation, according to the most recent protocols shared in North America. This article provides a review of the non-traditional anticoagulation strategies utilized in pediatric MCS, focusing on pharmacodynamics, indications, doses, and monitoring aspects of bivalirudin. Moreover, it exposes the efforts and the collaborations among different specialized centers, which are committed to an ongoing learning in order to minimize major complications in this special pediatric population. Further prospective trials regarding DTIs in a pediatric MCS setting are necessary and in specific well-designed randomized control trials between UFH and bivalirudin. To conclude, based on the reported literature, the clinical use of the bivalirudin in pediatric MCS seems to be a value added in controlling and maybe reducing thromboembolic complications. Further research is necessary to confirm all the results provided by this literature review.
View details for DOI 10.3389/fcvm.2021.671241
View details for Web of Science ID 000696727800001
View details for PubMedID 34540910
View details for PubMedCentralID PMC8440876
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Telemedicine for adult congenital heart disease patients during the first wave of COVID-19 era: a single center experience
JOURNAL OF CARDIOVASCULAR MEDICINE
2021; 22 (9): 706-710
Abstract
To summarize our experience on the implementation of a telemedicine service dedicated to adult congenital heart disease (ACHD) patients during the lockdown for the first wave of Coronavirus disease 2019 (COVID-19).This is a prospective study enrolling all ACHD patients who answered a questionnaire dedicated telematic cardiovascular examination.A total of 289 patients were enrolled, 133 (47%) were male, 25 (9%) were affected by a genetic syndrome. The median age was 38 (29-51) years, whereas the median time interval between the last visit and the telematic follow-up was 9.5 (7.5-11.5) months. Overall, 35 patients (12%) reported a worsening of fatigue in daily life activity, 17 (6%) experienced chest pain, 42 (15%) had presyncope and 2 (1%) syncope; in addition, 28 patients (10%) presented peripheral edema and 14 (5%) were orthopneic. A total of 116 (40%) patients reported palpitations and 12 had at least one episode of atrial fibrillation and underwent successful electrical (8) or pharmacological (4) cardioversion. One patient was admitted to the emergency department for uncontrolled arterial hypertension, five for chest pain, and one for heart failure. Two patients presented fever but both had negative COVID-19 nasal swab.During the COVID-19 pandemic, the use of telemedicine dramatically increased and here we report a positive experience in ACHD patients. The postpandemic role of telemedicine will depend on permanent regulatory solutions and this early study might encourage a more systematic telematic approach for ACHD patients.
View details for DOI 10.2459/JCM.0000000000001195
View details for Web of Science ID 000678208500006
View details for PubMedID 33882538
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Use of Transcarotid IMPELLA 2.5 Axial-Flow Pump Device for Left Ventricle Unloading During VA-ECMO Support in Pediatric Acute Heart Failure
WORLD JOURNAL FOR PEDIATRIC AND CONGENITAL HEART SURGERY
2021; 12 (4): 542-546
Abstract
An alternative strategy for left ventricular (LV) venting during short-term mechanical circulatory support is use of Impella axial-flow pump. We present our transcarotid Impella 2.5 implantation technique using a polytetrafluoroethylene graft, in two children with acute heart failure treated primarily with venoarterial ECMO. The venoarterial extracorporeal membrane oxygenator and Impella support were maintained for 5 and 17 days, respectively. Transcarotid Impella implantation might be an alternative and feasible option in pediatrics patients affected by severe LV failure, as a bridge to decision or bridge to candidacy. Potentially, the Impella 2.5 device provides less invasive support for children with heart failure.
View details for DOI 10.1177/21501351211017866
View details for Web of Science ID 000674725600017
View details for PubMedID 34278855
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ISHLT consensus statement for the selection and management of pediatric and congenital heart disease patients on ventricular assist devices Endorsed by the American Heart Association.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
2021
View details for DOI 10.1016/j.healun.2021.04.015
View details for PubMedID 34193359
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Deciphering Genetic Variants of Warfarin Metabolism in Children With Ventricular Assist Devices
PEDIATRIC CARDIOLOGY
2021; 42 (5): 1082-1087
Abstract
Warfarin is prescribed in patients with ventricular assist devices (VADs). Dosage depends on several factors including the underlying genotype. These include polymorphisms of genes encoding cytochrome P450 enzymes, the main ones being CYP2C9, VKORC1, and CYP4F2. The objectives of this study were to evaluate the prevalence of CY2CP9 1*2*3*, VKORC1, and CYP4F2 in children with VADs and the time to reach the target international normalized ratio. We performed a retrospective/prospective study in children with VADs. We recorded polymorphisms, disease, type of VAD, ethnicity, age, gender, height, weight, INR values, bleeding, and thromboembolic episodes. Informed consent was obtained. We enrolled 34 children (19 male, 15 female), with a median age of 2 years (range 0.3-17 years) and median weight of 6.9Kg. The Berlin Heart was the most commonly implanted VAD (22/34; 64%), and the most common diagnosis was dilated cardiomyopathy. Statistical analysis confirmed a significant partial correlation with VKORC1 CC (p = 0.019). The CYP2C9*2 CT genotype showed a late rise in target INR values (p = 0.06), while the CYP2C9*2 CC showed a tendency toward an early INR rise (p = 0.024). We provide new information on the contribution of the warfarin polymorphisms in children with VAD implantation. Pharmacogenomic dosing for children using warfarin has the potential to improve clinical care in VAD patients. Patients with the CYP2C9*2 CT genotype may need more time or higher doses to reach target INR, while clinicians may need to be aware of the potential for a rapid rise in INR in patients with the CYP2C9*2 CC genotype.
View details for DOI 10.1007/s00246-021-02585-2
View details for Web of Science ID 000638870600002
View details for PubMedID 33837838
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Proteomic Profile in Children and Young Adult Patients with Pulmonary Hypertension Due to Complex Congenital Heart Disease: An Observational Cohort Study
ELSEVIER SCIENCE INC. 2021: S463-S464
View details for Web of Science ID 000631254401401
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Preliminary Data on the Clinical Use of Infant Jarvik 2015 in Children with Dilated Cardiomyopathy; Recovery Will Be the New Therapeutic Goal?
ELSEVIER SCIENCE INC. 2021: S175
View details for Web of Science ID 000631254400393
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Single Center Experience with the Heartmate 3 Continuous-Flow Ventricular Assist Device in Pediatric Patients
ELSEVIER SCIENCE INC. 2021: S443
View details for Web of Science ID 000631254401353
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Use of carotid artery cannulation during redo sternotomy in congenital cardiac surgery: a single-centre experience
INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY
2021; 33 (1): 119-123
Abstract
Management of resternotomy is often a difficult challenge in patients with congenital diseases who have undergone multiple sternotomies. Our goal was to report our single-centre experience with carotid cannulation using a graft interposed during redo sternotomy in complex cardiac reintervention procedures.We performed a retrospective review of all patients who had undergone complex redo sternotomies between January 2019 and May 2020 utilizing a cervical cannulation technique with a Gore-Tex graft interposed on the carotid artery. We classified our population study on the basis of the primary diagnosis and the type of surgery. The primary outcomes of our analysis were the evaluation of the safety of the procedure in terms of survival and freedom from neurological events.We analysed 22 patients who had undergone previous complex operations. The median age and weight at the time of reintervention were 130.35 (range 0.46-435) months and 31.5 (range 2.2-85) kg, respectively. Composite graft carotid cannulation provided adequate arterial flow in all patients with a median arterial flow of 3.5 l/min/m2 (range 0.6-6). One major cardiac injury occurred during sternotomy when emergency cardiopulmonary bypass (CPB) was initiated. Moreover, during their hospital stays, all patients had an uneventful recovery without neurological or vascular complications and no cervical wound infections.Carotid cannulation using interposition of a side graft on the common carotid artery for arterial inflow is a reliable and safe method for initiation of CPB in complex redo surgeries in patients with congenital disease. Complications directly associated with this type of cannulation are uncommon and allow surgical re-entry with overall low risks.
View details for DOI 10.1093/icvts/ivab060
View details for Web of Science ID 000670960600016
View details for PubMedID 33704457
View details for PubMedCentralID PMC8691509
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Infant miniaturized continuous-flow pumps and permanent support in Pediatrics
ANNALS OF CARDIOTHORACIC SURGERY
2021; 10 (2): 278-280
View details for DOI 10.21037/acs-2020-cfmcs-15
View details for Web of Science ID 000636452900011
View details for PubMedID 33842224
View details for PubMedCentralID PMC8033256
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Neonatal respiratory and cardiac ECMO in Europe
EUROPEAN JOURNAL OF PEDIATRICS
2021; 180 (6): 1675-1692
Abstract
Neonatal extracorporeal membrane oxygenation (ECMO) is a life-saving procedure for critically ill neonates suffering from a potentially reversible disease, causing severe cardiac and/or respiratory failure and refractory to maximal conventional management. Since the 1970s, technology, management, and clinical applications of neonatal ECMO have changed. Pulmonary diseases still represent the principal neonatal diagnosis, with an overall 74% survival rate, and up to one-third of cases are due to congenital diaphragmatic hernia. The overall survival rate in cardiac ECMO is lower, with congenital heart defect representing the main indication. This review provides an overview of the available evidence in the field of neonatal ECMO. We will address the changing epidemiology, basic principles, technologic advances in circuitry, and monitoring, and deliver a current multidisciplinary management framework, focusing on ECMO applications, complications, and long-term morbidities. Lastly, areas for further research will be highlighted.Conclusions: ECMO is a life support with a potential impact on long-term patients' outcomes. In the next years, advances in knowledge, technology, and expertise may push neonatal ECMO boundaries towards more premature and increasingly complex infants, with the final aim to reduce the burden of ECMO-related complications and improve overall patients' outcomes. What is Known: • ECMO is a life-saving option in newborns with refractory respiratory and/or cardiac failure. • The multidisciplinary ECMO management is challenging and may expose neonates to complications with an impact on long-term outcomes. What is New: • Advances in technology and biomaterials will improve neonatal ECMO management and, eventually, the long-term outcome of these complex patients. • Experimental models of artificial placenta and womb technology are under investigation and may provide clinical translation and future research opportunities.
View details for DOI 10.1007/s00431-020-03898-9
View details for Web of Science ID 000615129300001
View details for PubMedID 33547504
View details for PubMedCentralID PMC7864623
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Long-term veno-arterial extracorporeal membrane oxygenation as a bridge to heart-lung transplant
JOURNAL OF CARDIAC SURGERY
2021; 36 (3): 798-799
Abstract
En bloc heart-lung transplantation still represents definitive therapy for end-stage cardiopulmonary failure. However, patients may critically decompensate while awaiting suitable donor organs and necessitate veno-arterial extracorporeal membrane oxygenation. In this article, we describe the combined use of central cannulation with the Berlin Heart EXCOR ventricular assist device cannulae and the CentriMag centrifugal pump as an extended bridge to heart-lung transplantation in three pediatric patients.
View details for DOI 10.1111/jocs.15369
View details for Web of Science ID 000612188200001
View details for PubMedID 33503686
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Left atrial strain highly correlates with left ventricular end-diastolic pressure in paediatric patients with heart transplant
OXFORD UNIV PRESS. 2020: N31-N32
View details for Web of Science ID 000614681700092
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Changes in circulating levels and cardiac expression of adiponectin system in children with heart failure after Ventricular Assist Device support
OXFORD UNIV PRESS. 2020: 1100
View details for Web of Science ID 000606106301103
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Pathophysiology and molecular signalling in pediatric heart failure and VAD therapy
CLINICA CHIMICA ACTA
2020; 510: 751-759
Abstract
Heart Failure (HF) is a progressive clinical syndrome characterized by molecular and structural abnormalities that result in impaired ventricular filling and a reduced blood ejection. In pediatric patients, HF represents an important cause of morbidity and mortality, but underlying cause, presentation and disease course remains unclear in many cases. It is evident that a child is not a "small adult" and findings are not comparable. The adoption of a standardized clinical and surgical tools as well as increased biomolecular research and therapeutic trials targeting pediatric patients with HF would greatly improve the management of this special class of patients. This review examines the most current information about the pathophysiology and molecular mechanisms related to HF in children to identify gaps in our knowledge base to further improve clinical care and outcomes.
View details for DOI 10.1016/j.cca.2020.09.010
View details for Web of Science ID 000582504300119
View details for PubMedID 32949569
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Persistent myocardial atrophy despite LV reverse remodeling in Duchenne cardiomyopathy treated by LVAD
PEDIATRIC TRANSPLANTATION
2021; 25 (2): e13890
Abstract
DCM is the leading cause of death in Duchenne patients. LVADs are considered as therapeutic options as DT in advanced HF. The aim of our study was to evaluate LV remodeling of Duchenne after LVADs and chronic therapy. Demographic and echocardiographic data of 8 Duchenne patients implanted with LVADs were reviewed and analyzed. All measures were collected before LVAD implantation, after 1 month and 1 year. All patients were affected by end-stage DCM, and mean age at implantation was 16.9 ± 2.9 years. Patients were treated with maximal medical therapy. One-year post-implantation HR decreased from a mean of 110 ± 19 bpm to 82 ± 2 bpm (P = .002), and a significant decrease in LV volumes and diameters LVEDD P = .03, LVESD P = .02, EDV P = .01, and ESV P = .02) was noticed together with a significant increase in EF (P = .0036). However, RWT did not change over time, showing an eccentric remodeling pattern pre- and post-LVADs. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function secondary to a significant ventricular unloading due to LVADs coupled with chronic therapy.
View details for DOI 10.1111/petr.13890
View details for Web of Science ID 000584301400001
View details for PubMedID 33105518
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Duchenne Dilated Cardiomyopathy: Cardiac Management from Prevention to Advanced Cardiovascular Therapies
JOURNAL OF CLINICAL MEDICINE
2020; 9 (10)
Abstract
Duchenne muscular dystrophy (DMD) cardiomyopathy (DCM) is characterized by a hypokinetic, dilated phenotype progressively increasing with age. Regular cardiac care is crucial in DMD care. Early recognition and prophylactic use of angiotensin converting enzyme inhibitors (ACEi) are the main stay therapeutic strategy to delay incidence of DMD-DCM. Pharmacological treatment to improve symptoms and left ventricle (LV) systolic function, have been widely implemented in the past years. Because of lack of DMD specific drugs, actual indications for established DCM include current treatment for heart failure (HF). This review focuses on current HF strategies to identify, characterize, and treat DMD-DCM.
View details for DOI 10.3390/jcm9103186
View details for Web of Science ID 000585090100001
View details for PubMedID 33019553
View details for PubMedCentralID PMC7600130
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Ethics and extracorporeal membrane oxygenation during coronavirus disease 2019 outbreak
PERFUSION-UK
2020; 35 (6): 562-564
View details for DOI 10.1177/0267659120937545
View details for Web of Science ID 000543449300001
View details for PubMedID 32580648
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Undiagnosed Severe Late Complications of Repaired Tetralogy of Fallot
CIRCULATION-CARDIOVASCULAR IMAGING
2020; 13 (6): e010273
View details for DOI 10.1161/CIRCIMAGING.119.010273
View details for Web of Science ID 000543399900009
View details for PubMedID 32482136
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Variations of circulating miRNA in paediatric patients with Heart Failure supported with Ventricular Assist Device: a pilot study
SCIENTIFIC REPORTS
2020; 10 (1): 5905
Abstract
Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.
View details for DOI 10.1038/s41598-020-62757-7
View details for Web of Science ID 000563491900002
View details for PubMedID 32246041
View details for PubMedCentralID PMC7125126
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Preliminary Data on the Clinical Use of Infant Jarvik 2015 in Children with Dilated Cardiomyopahty; Recovery Will Be the New Therapeutic Goal?
ELSEVIER SCIENCE INC. 2020: S221
View details for Web of Science ID 000522637201220
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Long-Term Outcome of LVAD in Duchenne Population with End Stage Cardiomyopathy
ELSEVIER SCIENCE INC. 2020: S219-S220
View details for Web of Science ID 000522637201216
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Left ventricular unloading during extracorporeal membrane oxygenation - Impella versus atrial septal defect: A simulation study
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
2020; 43 (10): 663-670
Abstract
Atrial septal defect and Impella have been proposed for left ventricular unloading in venoarterial extracorporeal membrane oxygenation patients. This work aims at evaluating the haemodynamic changes in venoarterial extracorporeal membrane oxygenation patients after Impella implantation or atrial septal defect realization by a simulation study.A lumped parameter model of the cardiovascular system was adapted to this study. Atrial septal defect was modelled as a resistance between the two atria. Venoarterial extracorporeal membrane oxygenation and Impella were modelled starting from their pressure-flow characteristics. The baseline condition of a patient undergoing venoarterial extracorporeal membrane oxygenation was reproduced starting from haemodynamic and echocardiographic data. The effects of different atrial septal defect size, Impella and venoarterial extracorporeal membrane oxygenation support were simulated.Impella caused an increment of mean arterial pressure up to 67%, a decrement in mean pulmonary arterial pressure up to 8%, a decrement in left ventricular end systolic volume up to 11% with a reduction up to 97% of left ventricular cardiac output. Atrial septal defect reduces left atrial pressure (19%), increases right atrial pressure (22%), increases mean arterial pressure (18%), decreases left ventricular end systolic volume (11%), increases right ventricular volume (33%) and decreases left ventricular cardiac output (55%).Impella has a higher capability in left ventricular unloading during venoarterial extracorporeal membrane oxygenation in comparison to atrial septal defect with a lower right ventricular overload.
View details for DOI 10.1177/0391398820906840
View details for Web of Science ID 000515029900001
View details for PubMedID 32089039
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Patient-specific Fluid Dynamical Evaluation of Hypoplastic Left Heart Syndrome Surgical Treatment
IEEE. 2020: 311-314
View details for DOI 10.1109/melecon48756.2020.9140649
View details for Web of Science ID 000783754700058
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ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
2020
Abstract
The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.
View details for DOI 10.1016/j.healun.2020.01.1345
View details for PubMedID 32088108
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Part VII: Behavioral economics-A framework for donor organ decision-making in pediatric heart transplantation.
Pediatric transplantation
2020: e13655
Abstract
The high discard rate of pediatric donor hearts presents a major challenge for children awaiting heart transplantation. Recent literature identifies several factors that contribute to the disparities in pediatric donor heart usage, including regulatory oversight, the absence of guidelines on pediatric donor heart acceptance, and variation among transplant programs. However, a likely additional contributor to this issue are the behavioral factors influencing transplant team decisions in donor offer scenarios, a topic that has not yet been studied in detail. Behavioral economics and decision psychology provide an excellent foundation for investigating decision-making in the pediatric transplant setting, offering key insights into the behavior of transplant professionals. We conducted a systematic review of published literature in pediatric heart transplant related to behavioral economics and the psychology of decision-making. In this review, we draw on paradigms from these two domains in order to examine how existing aspects of the transplant environment, including regulatory oversight, programmatic variation, and allocation systems, may precipitate potential biases surrounding donor offer decisions. Recognizing how human decision behavior influences donor acceptance is a first step toward improving utilization of potentially viable pediatric donor hearts.
View details for DOI 10.1111/petr.13655
View details for PubMedID 31985140
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Changes in left and right ventricular two-dimensional echocardiographic speckle-tracking indices in pediatric LVAD population: A retrospective clinical study
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
2019; 42 (12): 711-716
Abstract
Echocardiographic strain and strain-rate imaging is a promising tool for the evaluation of myocardial segmental function, for the early detection of myocardial dysfunction, and for the prediction of reverse remodeling. We aimed at studying the changes in left and right ventricular function in pulsatile left ventricular assist device pediatric patients by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography. Echocardiographic and clinical data of patients implanted with a pulsatile-flow left ventricular assist device from 2011 to 2018 were retrospectively reviewed before and after implantation at 1, 3, and 6 months. A total of 18 patients were enrolled. Median age and weight at implantation were 9 months (5-23 months) and 5.85 kg (4.85-8.75 kg), respectively; median left ventricular assist device support was 181 (114.5-289.5) days. 13 patients (73%) were transplanted and 5 patients (27%) died. At follow-up: left ventricular ejection fraction increase at 1 month (p = 0.001) and 3 months (p = 0.01), left ventricular global longitudinal strain improvement at 1 month (p = 0.0008) and 3 months (p = 0.02), and right ventricular free-wall longitudinal strain increase at 1 month (p = 0.01). At short term after left ventricular assist device implantation, both left ventricular and right ventricular mechanics improved. The temporary benefit seems to decrease over time. The worsening of left ventricular function has been followed by a worsening of right ventricular function probably due to the ventricular interdependence.
View details for DOI 10.1177/0391398819857446
View details for Web of Science ID 000493895600005
View details for PubMedID 31238772
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First human implantation of a miniaturized axial flow ventricular assist device in a child with end-stage heart failure.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
2019
View details for DOI 10.1016/j.healun.2019.09.003
View details for PubMedID 31761510
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Predicting the pressure of the total cavopulmonary connection: clinical testing of a mathematical equation
CARDIOLOGY IN THE YOUNG
2019; 29 (8): 1066-1071
Abstract
Some authors advocate the use of a dedicated formula to predict the Fontan pressure starting from pre-Fontan catheterisation data. This paper aims at testing the predictive value of the mentioned formula through a retrospective clinical study.Pre-Fontan catheterisation data and Fontan pressure measured at the completion were retrospectively collected. Pre-Fontan data were used to calculate the predicted pressure in the Fontan system. The predicted values were compared to the Fontan pressure measured at the Fontan completion and with the needs for fenestration. One hundred twenty-four Fontan patients were retrospectively enrolled (At Fontan: median age 30.73 [24.70-37.20] months, median weight 12.00 [10.98-14.15] kg). Fontan conduit was fenestrated in 78 patients. A poor correlation (r2 = 0.05128) between the measured and predicted data for non-fenestrated patients was observed. In the case of Fontan-predicted pressure <17.59 mmHg, the formula identified a good short-term clinical outcome with a sensitivity of 92%.The proposed formula showed a poor capability in estimating the actual pressure into the Fontan system and in identifying patients needing fenestration. As the pressure into the Fontan system is determined by multiple factors, the tested formula could be an additional data in a multi-parametric approach.
View details for DOI 10.1017/S1047951119001513
View details for Web of Science ID 000511211300011
View details for PubMedID 31331409
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Principlism and Personalism. Comparing Two Ethical Models Applied Clinically in Neonates Undergoing Extracorporeal Membrane Oxygenation Support
FRONTIERS IN PEDIATRICS
2019; 7: 312
Abstract
Extracorporeal membrane oxygenation (ECMO) is a technology used to temporarily assist critically ill patients with acute and reversible life-threatening cardiac and/or respiratory failure. This technology can often be lifesaving but is also associated with several complications that may contribute to reduced survival. Currently, neonates supported with ECMO are complex and bear an increased risk of mortality. This means that clinicians must be particularly prepared not only to deal with complex clinical scenarios, but also ethical issues associated with ECMO. In particular, clinicians should be trained to handle unsuccessful ECMO runs with attention to high quality end of life care. Within this manuscript we will compare and contrast the application of two ethical frameworks, used in the authors' institutions (Toronto and Rome). This is intended to enhance a broader understanding of cultural differences in applied ethics which is useful to the clinician in an increasingly multicultural and diverse patient mix.
View details for DOI 10.3389/fped.2019.00312
View details for Web of Science ID 000477817900001
View details for PubMedID 31417882
View details for PubMedCentralID PMC6682695
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Improvement of survival in low-weight children on the Berlin Heart EXCOR ventricular assist device support
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2019; 55 (5): 913-919
Abstract
Publications on the paediatric Berlin Heart EXCOR ventricular assist device have revealed that low body weight <10 kg is a significant risk factor for mortality with children weighing <5 kg being at the highest risk. However, these studies are limited to implantation periods prior to 2011. Since then, progress has been made in the optimization of patient selection and management. This study investigated whether the survival of children weighing <10 kg supported with the EXCOR assist device has improved in recent years and sought to determine the risk factors for mortality.The Berlin Heart EXCOR prospective registry (n = 1832) was retrospectively reviewed between 2000 and 2017 to compare the outcomes of different weight cohorts: A (<5 kg; n = 204), B (5-10 kg; n = 633) and C (>10 kg; n = 995) in different eras [era 1: January 2000-December 2012 (n = 1089) and era 2: January 2013-June 2017 (n = 743)].Overall survival in groups A and B significantly increased from era 1 to era 2 (group A 51% vs 65%, P < 0.001; group B 74% vs 78%, P = 0.001), whereas it remained stable in group C (78% vs 73%). In era 2, the survival of group B was not significantly different from group C. On the multivariable analysis of children weighing <5 kg, congenital heart disease, preoperative extracorporeal life support and biventricular support were independently associated with increased mortality in era 1 [hazard ratio 2.04 (95% confidence interval 1.18-3.53); 2.44 (1.36-4.37) and 1.93 (1.11-3.34), respectively] but not in era 2.Paediatric EXCOR ventricular assist device therapy has significantly improved for patients weighing <10 kg. Withholding a ventricular assist device is not justified on the basis of the body weight alone.
View details for DOI 10.1093/ejcts/ezy394
View details for Web of Science ID 000484087700017
View details for PubMedID 30590433
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Heart rate reduction strategy using ivabradine in end-stage Duchenne cardiomyopathy
INTERNATIONAL JOURNAL OF CARDIOLOGY
2019; 280: 99-103
Abstract
End-stage dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in patients with Duchenne Muscular Dystrophy (DMD). No studies are available on the effect of ivabradine on long-term outcomes in end-stage DMD/DCM.We prospectively enrolled a cohort of end-stage DMD/DCM patients with LV ejection fraction <40%, on chronic HF treatment with an ACE inhibitor referred consecutively from 2012 to 2017 to Bambino Gesù Children's Hospital. In each patient, before starting HRR strategy and after 1 year, we collected medical records comprehensive of clinical, demographic and imaging parameters, BNP levels, neurological and respiratory assessment.Twenty male patients with DMD/DCM with a mean age of 15.0 ± 3.5 (13-19 IQR) years were enrolled and divided into 2 groups according to ivabradine therapy. This group showed a higher incidence of MACEs compared to others in treatment with ivabradine (87.5% vs 12.5%, p = 0.025). At Kaplan Meier survival analysis curves, the rate free from MACEs was higher in patients treated with ivabradine (log rank p = 0.017). At multivariate Cox regression analysis, ivabradine therapy was an independent predictor of freedom from MACEs (H.R. 0.078, 95% CI 0.007-0.877, p = 0.039).HRR strategy, whether achieved by beta blockers alone or in combination with ivabradine, seemed to be effective in reducing the incidence of acute adverse events, reaching optimal target heart rate and improving left ventricular function in DMD/DCM patients.
View details for DOI 10.1016/j.ijcard.2019.01.052
View details for Web of Science ID 000458491600024
View details for PubMedID 30686494
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Is the New Infant Jarvik 2015 Suitable for Patients
ARTIFICIAL ORGANS
2019; 43 (1): E1-E8
Abstract
Our aim was to study the feasibility of implanting the Infant Jarvik 2015 in patients weighing less than 8 kg. The Infant Jarvik 2015 left ventricular assist device (LVAD) was tested in a hybrid simulator of the cardiovascular system reproducing specific patients' hemodynamics for different patient weights (2-7 kg). For each weight, the sensitivity of the pump to different circulatory parameters (peripheral resistance, left ventricular elastance, right ventricular elastance, heart rate, and heart filling characteristics) has been tested repeating for each experiment a pump ramp (10 000-18 000 rpm). The increase in the pump speed causes a decrease (increase) in the left (right) atrial pressure, an increase (decrease) in the arterial systemic (pulmonary) pressure, an increase in the right ventricular pressure, a decrease (increase) in the left (right) ventricular volume, a decrease in the left ventricular cardiac output, an increase in the LVAD output and an increase in the right ventricular cardiac output (total cardiac output). Suction was observed for lower weight patients and for higher pump speed in the case of vasodilation, left ventricular recovery, bradycardia, right ventricular failure, and left ventricular hypertrophy. Backflow was observed in the case of left ventricular recovery at lower pump speed. In the hybrid simulator, the Infant Jarvik 2015 could be suitable for the implantation in patients lower than 8 kg because of the stability of the device respect to the cardio/circulatory changes (low frequency of suction and backflow) and because of the capability of the device to maintain adequate patient hemodynamics.
View details for DOI 10.1111/aor.13302
View details for Web of Science ID 000457064000001
View details for PubMedID 30398290
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Profiles of heart failure in adolescents and young adults with congenital heart disease
PROGRESS IN PEDIATRIC CARDIOLOGY
2018; 51: 37-45
View details for DOI 10.1016/j.ppedcard.2018.10.005
View details for Web of Science ID 000451752200007
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The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): first EUROMACS Paediatric (Paedi-EUROMACS) report
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2018; 54 (5): 800-808
Abstract
EUROMACS is a registry of the European Association for Cardio-Thoracic Surgery (EACTS) whose purpose is to gather clinical data related to durable mechanical circulatory support for scientific purposes and to publish annual reports. Because the treatment of children with end-stage heart failure has several significantly different characteristics than the treatment of adults, data and outcomes of interventions are analysed in this dedicated paediatric report.Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (≤19 years of age) performed from 1 January 2000 to 31 December 2017 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events.Twenty-five hospitals contributed 237 registered implants in 210 patients (81 ♀, 129 ♂) to the registry. The most frequent diagnosis was any form of cardiomyopathy (71.4%) followed by congenital heart disease (18.6%). Overall mean support time on a device was 11.6 months (±16.5 standard deviation). A total of 173 children (82.4%) survived to transplant, recovery or are ongoing; 37 patients (17.6%) died while on support within the observed follow-up time. At 12 months 38% of patients received transplants, 7% were weaned from their device and 15% died. At 24 months, 51% of patients received transplants, 17% died while on support, 22% were on a device and 9% were explanted due to myocardial recovery. The adverse events rate per 100 patient-months was 11.97 for device malfunction, 2.83 for major bleeding, 2.83 for major infection and 1.52 for neurological events within the first 3 months after implantation.The first paediatric EUROMACS report reveals a low transplant rate in European countries within the first 2 years of implantation compared to US data. The 1-year survival rate seems to be satisfactory. Device malfunction including pump chamber changes due to thrombosis was the most frequent adverse event.
View details for DOI 10.1093/ejcts/ezy298
View details for Web of Science ID 000456105500002
View details for PubMedID 30184070
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Time-course of circulating cardiac and inflammatory biomarkers after Ventricular Assist Device implantation: Comparison between paediatric and adult patients
CLINICA CHIMICA ACTA
2018; 486: 88-93
Abstract
Ventricular Assist Device (VAD) as bridge to transplantation is a common therapy for adult with heart failure (HF), but VAD use is increasing also in children. Cardiac and inflammatory biomarkers have an important role in the diagnosis and prognosis of HF in adults, but their role in paediatric setting is unknown. The aim of this study was to examine changes in cardiac and inflammatory biomarkers, both in HF paediatric and adult patients, before and following VAD.Cardiac (NT-proBNP, cTnI, sST2,Gal-3) and inflammatory (IL-6,IL-8) biomarkers were determined in plasma collected from 12 paediatric patients and 7 adult patients with HF, before and at 4 h,1,3,7,14 and 30 days after VAD implant.All biomarkers increased up to 1 day after VAD implant and then decreased at pre-VAD levels in 1 month in both groups. Only in children, NT-proBNP decreased significantly after 30 days Post-VAD treatment compared to pre-VAD levels. During the post-operative time-course, NT-proBNP and sST2 were significantly higher in children than adults, while IL-6 was lower.Cardiac and inflammatory biomarkers were differently modified by VAD implant in children compared to adults. These preliminary data could suggest that different molecular pathways may underlie HF patho-physiology of the two groups, possibly paving the way to a specific and targeted therapeutic intervention in the near future.
View details for DOI 10.1016/j.cca.2018.07.036
View details for Web of Science ID 000447481400016
View details for PubMedID 30040920
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First evidence of maternally inherited mosaicism in <i>TGFBR1 </i>and subtle primary myocardial changes in Loeys-Dietz syndrome: a case report
BMC MEDICAL GENETICS
2018; 19: 170
Abstract
Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far.This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.
View details for DOI 10.1186/s12881-018-0661-2
View details for Web of Science ID 000444899000001
View details for PubMedID 30219046
View details for PubMedCentralID PMC6139163
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Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine
JOURNAL OF CLINICAL MEDICINE
2018; 7 (9)
Abstract
Duchenne's muscular dystrophy is an X-linked neuromuscular disease that manifests as muscle atrophy and cardiomyopathy in young boys. However, a considerable percentage of carrier females are often diagnosed with cardiomyopathy at an advanced stage. Existing therapy is not disease-specific and has limited effect, thus many patients and symptomatic carrier females prematurely die due to heart failure. Early detection is one of the major challenges that muscular dystrophy patients, carrier females, family members and, research and medical teams face in the complex course of dystrophic cardiomyopathy management. Despite the widespread adoption of advanced imaging modalities such as cardiac magnetic resonance, there is much scope for refining the diagnosis and treatment of dystrophic cardiomyopathy. This comprehensive review will focus on the pertinent clinical aspects of cardiac disease in muscular dystrophy while also providing a detailed consideration of the known and developing concepts in the pathophysiology of muscular dystrophy and forthcoming therapeutic options.
View details for DOI 10.3390/jcm7090291
View details for Web of Science ID 000445635800065
View details for PubMedID 30235804
View details for PubMedCentralID PMC6162458
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<i>Comment on:</i> 'Implantation of a left ventricular assist device to provide long term support for end-stage Duchenne muscular dystrophy-associated cardiomyopathy' by Stoller <i>et al</i>.
ESC HEART FAILURE
2018; 5 (4): 651-652
View details for DOI 10.1002/ehf2.12286
View details for Web of Science ID 000440649400014
View details for PubMedID 29931760
View details for PubMedCentralID PMC6073016
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Antithrombotic therapy in pediatric ventricular assist devices: Multicenter survey of the European EXCOR Pediatric Investigator Group
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
2018; 41 (7): 385-392
Abstract
Mechanical circulatory support for pediatric heart failure patients with the Berlin Heart EXCOR ventricular assist system is the only approved and established bridging strategy for recovery or heart transplantation. In recent years, the burden of thromboembolic events has led to modifications of the recommended antithrombotic therapy. Therefore, we aimed to assess modifications of antithrombotic practice among the European EXCOR Pediatric Investigator Group members.We sent a questionnaire assessing seven aspects of antithrombotic therapy to 18 European hospitals using the EXCOR device for children. Returned questionnaires were analyzed and identified antithrombotic strategies were descriptively compared to "Edmonton protocol" recommendations developed for the US EXCOR pediatric approval study.Analysis of 18 received surveys revealed substantial deviations from the Edmonton protocol, including earlier start of heparin therapy at 6-12 h postoperatively and in 50% of surveyed centers, monitoring of heparin effectiveness with aPTT assay, administering vitamin K antagonists before 12 months of age. About 39% of centers use higher international normalized ratio targets, and platelet inhibition is changed in 56% including the use of clopidogrel instead of dipyridamole. Significant inter-center variability with multiple deviations from the Edmonton protocol was discovered with only one center following the Edmonton protocol completely.Current antithrombotic practice among European EXCOR users representing the treatment of more than 600 pediatric patients has changed over time with a trend toward a more aggressive therapy. There is a need for systematic evidence-based evaluation and harmonization of developmentally adjusted antithrombotic management practices in prospective studies toward revised recommendations.
View details for DOI 10.1177/0391398818773040
View details for Web of Science ID 000436072700004
View details for PubMedID 29749291
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The first five years of neonatal and pediatric transports on extracorporeal membrane oxygenation in the center and south of Italy: The pediatric branch of the Italian "Rete Respira" network
SAGE PUBLICATIONS LTD. 2018: 24-30
Abstract
Neonatal and pediatric ECMO is a high-risk procedure that should be performed only in expert centers. Children who are eligible for ECMO and are managed in hospitals without ECMO capabilities should be referred to the closest ECMO center before the severity of illness precludes safe conventional transport. When the clinical situation precludes safe conventional transport, ECMO should be provided on site with the patient transported on ECMO.We retrospectively reviewed our institutional database of all ECMO transports for neonatal and pediatric respiratory failure from February 2013 to February 2018.Over the last 5 years, we provided 24 transports covering all requests from the center and south of Italy except for the islands. Of these transports, 20 were performed on ECMO and 4 without ECMO. No patient died during transportation. Five complications were reported only during the ECMO transports, and all of these were managed without compromising the patient's safety. The preferred modes of transport were by ambulance (70%) and ambulance transported into the fixed wing aircraft (30%) for longer national distances. The survival to hospital discharge of the patients transported with ECMO was 75% among the neonatal transports and 83.3% among the pediatric transports. The survival to hospital discharge of the four patients transported without ECMO was 100% for both neonates and children.Neonatal and pediatric ECMO transports can be safely performed with a dedicated team that maintains stringent adherence to well-designed management protocols.
View details for DOI 10.1177/0267659118766829
View details for Web of Science ID 000432998400004
View details for PubMedID 29788844
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A New 2D Echocardiographic Approach to Evaluate the Membrane and Valve Movement of the Berlin Heart EXCOR VAD Chamber in Pediatric VAD Patients
WILEY. 2018: 451-456
Abstract
The use of Berlin Heart EXCOR VAD (BH) is a validated therapy to bridge pediatric patients to heart transplant. Serial echocardiographic (ECHO) assessment of VAD patients is necessary to support patients' management. This work aims at developing an innovative strategy to evaluate the BH device functioning by ECHO and its interaction with the native heart in a pediatric population. ECHO evaluation of BH membrane movement, and inflow and outflow valves was performed in 2D, 2D-color Doppler, M-mode, and M-mode color Doppler to assess the functioning of the device by direct positioning of the ECHO probe on the BH cannulas and membranes. Forty Berlin Heart EXCOR VAD were analyzed in 18 patients. Seven BH were placed as RVAD and 33 as LVAD. Results evidenced that 14 (21) inflow (outflow) valves presented a mild regurgitation, while 5 inflow (3 outflow) valves presented a moderate regurgitation. In three cases, we observed severe valve regurgitation with back flow in the left ventricle/right atrium. In both cases, the BH chambers were substituted, but we observed that in one case the regurgitation was due to cannulas compression, while in the other case it was due to valve malfunctioning. The M-mode and the ECHO of the membranes and valves permitted to appreciate the beat phenomenon to assess if the native heart and the BH are working in opposite or in the same phase. The membrane ECHO permits evaluation of minimal changes in membrane movement to assure the completely empty-completely fully work modality. Systematic ECHO assessment of BH chamber might support the BH programming and the detection of anomalous VAD-heart interaction.
View details for DOI 10.1111/aor.13122
View details for Web of Science ID 000430277400012
View details for PubMedID 29667250
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Evolution of Biventricular Loading Condition in Pediatric LVAD Patient: A Prospective and Observational Study
WILEY. 2018: 386-393
Abstract
The aim of this study was to describe the echocardiographic trend of left ventricular (LV) and right ventricular (RV) function after implantation of a pulsatile flow left ventricular assist device (LVAD) in children. From 2013 to 2016, we prospectively evaluated 13 consecutive pediatric Berlin Heart EXCOR LVAD patients. Clinical and echocardiographic data were collected at baseline, within 24 h after implantation and monthly until LVAD explant. Median age and weight at the implantation was 8 (4-23) months and 5 (4.6-8.3) kg at the time of implantation, respectively. All were affected by dilated cardiomyopathy. Average LVAD support time was 226.2 ± 121.2 days. Nine (70%) were transplanted, 4 (30%) died. LV end-systolic and end-diastolic volumes were reduced until the follow up of two months (P = 0.019 and P = 0.001). A progressive increase in RV dimensions was observed. After 4 months of follow up, RV fractional area change worsening was statistically related with the deterioration of LV unloading (P = 0.0036). Four patients needed prolonged inotropic support for RV failure. Pulsatile LVAD in pediatrics is followed by an early and mid-term LV unloading, as expressed by a decrease in LV volumes and diameters at echocardiogram. The effects of unloading do not remain stable at long term follow up. RV function improved in the acute phase, but a progressive dilatation of RV was noted over time. In some patients, RV failure might lead to the need of an increase of inotropic support at long term follow up.
View details for DOI 10.1111/aor.13050
View details for Web of Science ID 000430277400005
View details for PubMedID 29230826
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Acute and Long-Term Effects of LVAD Support on Right Ventricular Function in Children with Pediatric Pulsatile Ventricular Assist Devices
ASAIO JOURNAL
2018; 64 (1): 91-97
Abstract
Right ventricular failure (RVF) is a significant issue when considering left ventricular assist device (LVAD) implantation in pediatrics. The aim of this study was to evaluate the effects of LVAD on right ventricular (RV) function in children. We retrospectively reviewed clinical and echocardiographic data of children who underwent Berlin Heart EXCOR LVAD focusing on RV function before and after implantation (1, 3, and 6 month follow-up). An isolated LVAD was used in 27 patients. Median age was 11 months (interquartile range [IQR]: 5-24 months), with a median weight of 6.3 kg (IQR: 5-9 kg). Median time on ventricular assist device (VAD) support was 147 days (IQR: 86-210 days). Twenty patients were successfully bridged to orthotopic heart transplantation (OHT) (74%), six patients died (22%), and also heart function recovered in one patient (4%). Before LVAD implantation, nine patients (33%) showed a RV fractional area change (RVFAC) less than or equal to 30%. After implantation, mean RVFAC increased up until the 3 month follow-up (43.13%; p = 0.033) and then slightly decreased. In a subgroup of 18 patients, the average strain value increased after the 1 month follow-up (p = 0.022). Right ventricular failure developed in 33% of patients before the 1 month follow-up, and 7.4% experienced RVF at the 6 month follow-up. No patient required biventricular assist device (BiVAD). In our population, pulsatile-flow LVAD in children allows optimal RV decompression and function post-LVAD as measured by improvement in RV function at echo particularly at 1 and 3 month follow-up. At long-term follow-up, the beneficial effects of LVAD on RV function seem to be reduced as signs and symptoms of late RVF may develop in some patients despite LVAD support.
View details for DOI 10.1097/MAT.0000000000000596
View details for Web of Science ID 000428887200017
View details for PubMedID 28509675
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Control of a Pediatric Pulsatile Ventricular Assist Device: A Hybrid Cardiovascular Model Study
ARTIFICIAL ORGANS
2017; 41 (12): 1099-1108
Abstract
The aim of this work is to study pediatric pneumatic ventricle (PVAD) performance, versus VAD rate (VADR) and native heart rate (HR) ratio Rr (VADR/HR). The study uses a hybrid model of the cardiovascular system (HCS). HCS consists of a computational part (a lumped parameter model including left and right ventricles, systemic and pulmonary arterial and venous circulation) interfaced to a physical part. This permits the connection of a VAD (15 mL PVAD). Echocardiographic and hemodynamic data of a pediatric patient (average weight 14.3 kg, HR 100 bpm, systemic pressure 75/44 mm Hg, CO 1.5 L/min) assisted apically with asynchronous PVAD were used to set up a basal condition in the model. After model tuning, the assistance was started, setting VAD parameters (ejection and filling pressures, systole duration) to completely fill and empty the PVAD. The study was conducted with constant HR and variable VADR (50-120, step 10, bpm). Experiments were repeated for two additional patients' HRs, 90 and 110 bpm and for two values of systemic arterial resistance (Ras ) and Emax . Experimental data were collected and stored on disk. Analyzed data include average left and right ventricular volumes (LVV, RVV), left ventricular flow (LVF), VAD flow (VADF), and total cardiac output (COt). Data were analyzed versus Rr. LVV and RVV are sensitive to Rr and a left ventricular unloading corresponds in general to a right ventricular loading. In the case of asynchronous assistance, frequency beats are always present and the beat rate is equal to the difference between HR and VADR. In the case of pulsatile asynchronous LVAD assistance, VADR should be chosen to minimize frequency beat effects and right ventricular loading and to maximize left ventricular unloading.
View details for DOI 10.1111/aor.12929
View details for Web of Science ID 000417839800009
View details for PubMedID 28621816
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Evolution of Ventricular Energetics in the Different Stages of Palliation of Hypoplastic Left Heart Syndrome: A Retrospective Clinical Study
PEDIATRIC CARDIOLOGY
2017; 38 (8): 1613-1619
Abstract
Hyperplastic left heart syndrome (HLHS) patients are palliated by creating a Fontan-type circulation passing from different surgical stages. The aim of this work is to describe the evolution of ventricular energetics parameters in HLHS patients during the different stages of palliation including the hybrid, the Norwood, the bidirectional Glenn (BDG), and the Fontan procedures. We conducted a retrospective clinical study enrolling all HLHS patients surgically treated with hybrid procedure and/or Norwood and/or BDG and/or Fontan operation from 2011 to 2016 collecting echocardiographic and hemodynamic data. Measured data were used to calculate energetic variables such as ventricular elastances, external and internal work, ventriculo-arterial coupling and cardiac mechanical efficiency. From 2010 to 2016, a total of 29 HLHS patients undergoing cardiac catheterization after hybrid (n = 7) or Norwood (n = 6) or Glenn (n = 8) or Fontan (n = 8) procedure were retrospectively enrolled. Ventricular volumes were significantly higher in the Norwood circulation than in the hybrid circulation (p = 0.03) with a progressive decrement from the first stage to the Fontan completion. Ventricular elastances were lower in the Norwood circulation than in the hybrid circulation and progressively increased passing from the first stage to the Fontan completion. The arterial elastance and Rtot increased in the Fontan circulation. The ventricular work progressively increased. Finally, the ventricular efficiency improves passing from the first to the last stage of palliation. The use of ventricular energetic parameters could lead to a more complete evaluation of such complex patients to better understand their adaptation to different pathophysiological conditions.
View details for DOI 10.1007/s00246-017-1704-8
View details for Web of Science ID 000415580300012
View details for PubMedID 28831530
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Ventricular Energetics in Pediatric Left Ventricular Assist Device Patients: A Retrospective Clinical Study
ASAIO JOURNAL
2017; 63 (6): 815-823
Abstract
The aim of this study is to estimate the trend of right and left energetic parameters in left ventricular assist device (LVAD) pediatric patients. Echocardiographic data were retrospectively collected at the baseline, in the acute phase after and at the monthly follow-ups till the LVAD explantation to estimate left and right ventricular energetic parameters. A significant relationship between the left and right ventricular energetic parameter trends was found along all the study period. Left ventricular end-systolic pressure-volume relationship improved till the follow-up of 2 months and then progressively decreases. Left arteroventricular coupling decreases after the LVAD, and right arteroventricular coupling decreases at the short-term follow-up. Left ventricular external work, potential energy, and pressure-volume area decrease at the short-term follow-up and then increase progressively. Right ventricular external work, potential energy, and pressure-volume area increase after the LVAD implantation. Left (right) cardiac mechanical efficiency is improved (worsened) by the LVAD. Energetic variables show that the LVAD benefits could decrease over time. A continuous and patient tailored LVAD setting could contribute to prolong LVAD benefits. The introduction of energetic parameters could lead to a more complete evaluation of LVAD patients' outcome which is a multiparametric process.
View details for DOI 10.1097/MAT.0000000000000595
View details for Web of Science ID 000415716800023
View details for PubMedID 28514263
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A current approach to heart failure in Duchenne muscular dystrophy
HEART
2017; 103 (22): 1770-+
Abstract
Duchenne muscular dystrophy (DMD) is a genetic, progressive neuromuscular condition that is marked by the long-term muscle deterioration with significant implications of pulmonary and cardiac dysfunction. As such, end-stage heart failure (HF) in DMD is increasingly becoming the main cause of death in this population. The early detection of cardiomyopathy is often challenging, due to a long subclinical phase of ventricular dysfunction and difficulties in assessment of cardiovascular symptomatology in these patients who usually loose ambulation during the early adolescence. However, an early diagnosis of cardiovascular disease in patients with DMD is decisive since it allows a timely initiation of cardioprotective therapies that can mitigate HF symptoms and delay detrimental heart muscle remodelling. Echocardiography and ECG are standardly used for screening and detection of cardiovascular abnormalities in these patients, although these tools are not always adequate to detect an early, clinically asymptomatic phases of disease progression. In this regard, cardiovascular magnetic resonance (CMR) with late gadolinium enhancement is emerging as a promising method for the detection of early cardiac involvement in patients with DMD. The early detection of cardiac dysfunction allows the therapeutic institution of various classes of drugs such as corticosteroids, beta-blockers, ACE inhibitors, antimineralocorticoid diuretics and novel pharmacological and surgical solutions in the multimodal and multidisciplinary care for this group of patients. This review will focus on these challenges and available options for HF in patients with DMD.
View details for DOI 10.1136/heartjnl-2017-311269
View details for Web of Science ID 000414095500007
View details for PubMedID 28668906
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Welcome to the Thirteen International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion
ARTIFICIAL ORGANS
2017; 41 (9): 800-802
View details for DOI 10.1111/aor.13014
View details for Web of Science ID 000411067600008
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Closing the gap in paediatric ventricular assist device therapy with the Berlin Heart EXCOR® 15-ml pump
INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY
2017; 24 (5): 768-771
Abstract
The Berlin Heart EXCOR ® (EXCOR) paediatric ventricular assist device is used worldwide for mechanical support of infants and small children with end-stage heart failure. A clinically important gap between the smallest EXCOR blood pump (10 ml) and the next larger size (25 ml) limited the choice of pump size in patients with a body surface area (BSA) between 0.33 and 0.5 m 2 . We present the first clinical experience from the early product surveillance (EPS) of the new EXCOR 15-ml blood pump.After CE and U.S. Food and Drug Administration approval in January 2013, 20 patients with a mean age of 1.6 years (range 0.5-3.5 years) and a mean BSA of 0.45 m 2 (range 0.33-0.59 m 2 ) were enrolled in the EPS. The main diagnosis was idiopathic cardiomyopathy in 13 patients; the majority ( n = 16) of children were in INTERMACS level 1 or 2. Data from high-volume paediatric transplant centres were collected prospectively for a defined follow-up period of 60 days after device implantation.Mean time on the EXCOR 15-ml blood pump was 43 days; the survival rate was 100% at the end of the EPS period. Seven patients underwent a heart transplant from the device; 2 children were weaned; and 11 patients remained on support. Infection of cannula exit sites occurred in 3 patients. Two patients had minor thromboembolic strokes but made a complete neurological recovery.The new EXCOR 15-ml blood pump demonstrated optimal ventricular assist device support of children with a BSA of 0.33-0.5 m 2 .
View details for DOI 10.1093/icvts/ivw437
View details for Web of Science ID 000404044600020
View details for PubMedID 28453795
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Use of Simulation To Implement the Use of Helicopter for ECMO Transport
WILEY. 2017: 53-54
View details for Web of Science ID 000401006600145
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Evaluation of an "High Fidelity" Simulation Program for the ECMO Training of Nurses and Medical Staff in a Pediatric Intensive Care Unit: The Bambino Gesu Children's Hospital Experience
WILEY. 2017: 51-52
View details for Web of Science ID 000401006600140
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Pilot Study of Warfarin Genotype Polymorphisms in Pediatric Patients with Ventricular Assist Devices
ELSEVIER SCIENCE INC. 2017: S281
View details for Web of Science ID 000398839801008
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Application of a Lumped Parameter Model to Study the Feasibility of Simultaneous Implantation of a Continuous Flow Ventricular Assist Device (VAD) and a Pulsatile Flow VAD in BIVAD Patients
ARTIFICIAL ORGANS
2017; 41 (3): 242-252
Abstract
The aim of this work is to develop and test a lumped parameter model of the cardiovascular system to simulate the simultaneous use of pulsatile (P) and continuous flow (C) ventricular assist devices (VADs) on the same patient. Echocardiographic and hemodynamic data of five pediatric patients undergoing VAD implantation were retrospectively collected and used to simulate the patients' baseline condition with the numerical model. Once the baseline hemodynamic was reproduced for each patient, the following assistance modalities were simulated: (a) CVAD assisting the right ventricle and PVAD assisting the left ventricle (RCF + LPF), (b) CVAD assisting the left ventricle and PVAD assisting the right ventricle (LCF + RPF). The numerical model can well reproduce patients' baseline. The cardiac output increases in both assisted configurations (RCF + LPF: +17%, LCF + RPF: +21%, P = ns), left (right) ventricular volumes decrease more evidently in the configuration LCF + RPF (RCF + LPF), left (right) atrial pressure decreases in the LCF + RPF (RCF + LPF) modality. The pulmonary arterial pressure slightly decreases in the configuration LCF + RPF and it increases with RCF + LPF. Left and right ventricular external work increases in both configurations probably because of the total cardiac output increment. However, left and right artero-ventricular coupling improves especially in the LCF + RPF (-36% for the left ventricle and -21% for the right ventricle, P = ns). The pulsatility index decreases by 8.5% in the configuration LCF + RPF and increases by 6.4% with RCF + LPF (P = 0.0001). A numerical model could be useful to tailor on patients the choice of the VAD that could be implanted to improve the hemodynamic benefits. Moreover, a model could permit to simulate extreme physiological conditions and innovative configurations, as the implantation of both CVAD and PVAD on the same patient.
View details for DOI 10.1111/aor.12911
View details for Web of Science ID 000396014200005
View details for PubMedID 28281287
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Left ventricular assist device as destination therapy in cardiac end-stage dystrophinopathies: Midterm results
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2017; 153 (3): 669-674
Abstract
We report our experience with the use of a left ventricular assist device (LVAD) as destination therapy (DT) for the management of patients with cardiac end-stage dystrophinopathies.From February 2011 to February 2016, 7 patients with dystrophinopathies and dilated cardiomyopathy (DCM) were treated with LVADs at our institution. Median age at surgery was 16.5 years (range, 14.2-23.4 years). All patients were preoperatively evaluated by a multidisciplinary team approach.All patients survived to hospital discharge. The early postoperative course was characterized by abdominal bleeding (1 patient) and retropharyngeal bleeding (1 patient). Because of abdominal or retropharyngeal bleeding, both required postoperative heparin infusion discontinuation for 35 and 33 days, respectively. Among the late complications, 1 child developed osteolysis and infection at the pedestal site of the device, which required surgical displacement; 1 patient required gastrostomy as a result of poor feeding, and another had a cerebral stroke, which was treated with percutaneous thrombus aspiration. The other 2 patients did not show early or late complications. At a median follow-up time of 21.7 months (range, 3-45 months) there have been 3 deaths: 1 patient died of a lung infection after 45 months, 1 died of tracheal bleeding after 29 months, and 1 died of cerebral hemorrhage after 14 months.Our experience indicates that the use of an LVAD as DT in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options.
View details for DOI 10.1016/j.jtcvs.2016.08.016
View details for Web of Science ID 000397841200041
View details for PubMedID 27692952
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Concomitant pulsatile and continuous flow VAD in biventricular and univentricular physiology: a comparison study with a numerical model
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
2017; 40 (2): 74-81
Abstract
To develop and test a lumped parameter model to simulate and compare the effects of the simultaneous use of continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VADs) to assist biventricular circulation vs. single ventricle circulation in pediatrics.Baseline data of 5 patients with biventricular circulation eligible for LVAD and of 5 patients with Fontan physiology were retrospectively collected and used to simulate patient baselines. Then, for each patient the following simulations were performed: (a) CF VAD to assist the left ventricle (single ventricle) + a PF VAD to assist the right ventricle (cavo-pulmonary connection) (LCF + RPF); (b) PF VAD to assist the left ventricle (single ventricle) + a CF VAD to assist the right ventricle (cavo-pulmonary connection) (RCF + LPF).In biventricular circulation, the following results were found: cardiac output (17% RCF + LPF, 21% LCF + RPF), artero-ventricular coupling (-36% for the left ventricle and -21.6% for the right ventricle), pulsatility index (+6.4% RCF + LPF, p = 0.02; -8.5% LCF + RPF, p = 0.00009). Right (left) atrial pressure and right (left) ventricular volumes are decreased by the RCF + LPF (by RPF + LCF). Pulmonary arterial pressure decreases in the LCF + RPF configuration. In Fontan physiology: cardiac output (LCF + RPF 35% vs. 8% in RCF + LPF), ventricular preload (+4% RCF + LPF, -10% LCF + RPF), Fontan conduit pressure (-5% RCF + LPF, +7% LCF + RPF), artero-ventricular coupling (-14% RCF + LPF vs. -41% LCF + RPF) and pulsatility (+13% RCF + LPF, - 8% LCF + RPF).A numerical model supports clinicians in defining and innovating the VAD implantation strategy to maximize the hemodynamic benefits. Results suggest that the hemodynamic benefits are maximized by the LCF + RPF configuration.
View details for DOI 10.5301/ijao.5000562
View details for Web of Science ID 000400273300004
View details for PubMedID 28218352
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Concurrent Use of Continuous and Pulsatile Flow Ventricular Assist Device on a Fontan Patient: A Simulation Study
ARTIFICIAL ORGANS
2017; 41 (1): 32-39
Abstract
The aim of this work is to develop and test a lumped parameter model of the cardiovascular system to simulate the concurrent use of pulsatile (PVAD) and continuous flow (CVAD) ventricular assist device (VAD) on Fontan patients. Echocardiographic and hemodynamic data of five Fontan patients were retrospectively collected and used to simulate the patients' baseline hemodynamics. Then, for each patient, the following assistance modality was simulated for the cavopulmonary and the single ventricle (SV): (a) CVAD for cavopulmonary assistance (RCF) and PVAD assisting the SV (LCF) (RPF + LCF), (b) CVAD assisting SV and PVAD for cavopulmonary assistance (LPF + RCF). The numerical model can well reproduce patients' baseline. The cardiac output increases more importantly in the LCF + RPF configuration (35 vs. 8%). Ventricular volume decreases more evidently in the configuration LCF + RPF (28 vs. 6%), atrial pressure decreases in the LCF + RPF modality (10%), while it slightly increases in the RCF + LPF modality. The pulmonary arterial pressure slightly decreases (increases) in the configuration RCF + LPF (LCF + RPF). Ventricular external work increases in both configurations because of the total increment of the cardiac output. However, artero-ventricular coupling improves in both configurations: RCF + LPF-14%, LCF + RPF-41%. The pulsatility index decreases (increases) by 8% (13.8%) in the configuration LCF + RPF (RCF + LPF). A model could permit us to simulate extreme physiological conditions of the implantation of both CF and PF VAD on the Fontan patient and could permit to choose the proper VAD on the base of patients' condition. The configuration LCF + RPF seems to maximize the hemodynamic benefits.
View details for DOI 10.1111/aor.12859
View details for Web of Science ID 000393318500007
View details for PubMedID 28025826
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The Use of Berlin Heart EXCOR VAD in Children Less than 10 kg: A Single Center Experience
FRONTIERS IN PHYSIOLOGY
2016; 7: 614
Abstract
Objective: Despite the improvement in ventricular assist device (VAD) therapy in adults and in adolescents, in infant population only Berlin Heart EXCOR (BHE) is licensed as long term VAD to bridge children to Heart Transplantation (HTx). Particularly demanding in terms of morbidity and mortality are smallest patients namely the ones implanted in the first year of life or with a lower body surface area. This work aims at retrospective reviewing a single center experience in using BHE in children with a body weight under 10 kg. Methods: Data of all pediatric patients under 10 kg undergoing BHE implantation in our institution from March 2002 to March 2016 were retrospectively reviewed. Results: Of the 30 patients enrolled in the study, 53% were male, 87% were affected by a dilated cardiomyopathy with an average weight and age at the implantation of 6.75 ± 2.16 Kg and 11.57 ± 10.12 months, respectively. Three patients (10%) required a BIVAD implantation. After the implantation, 7 patients (23%) required re-intervention for bleeding and 9 patients (30%) experienced BHE cannulas infection. A total of 56 BHE pump were changed for thrombus formation (1.86 BHE pump for patient). The average duration of VAD support was 132.8 ± 94.4 days. Twenty patients (67%) were successfully transplanted and 10 patients (33%) died: 7 for major neurological complication and 3 for sepsis. Conclusion: Mechanical support in smaller children with end stage heart failure is an effective strategy for bridging patients to HTx. The need for BIVAD was relegated, in the last years, only to restrictive cardiomiopathy. Further efforts are required in small infants to improve anticoagulation strategy to reduce neurological events and BHE pump changes.
View details for DOI 10.3389/fphys.2016.00614
View details for Web of Science ID 000389378400001
View details for PubMedID 27999550
View details for PubMedCentralID PMC5138210
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The nuclear pore protein Nup153 associates with chromatin and regulates cardiac gene expression in dystrophic <i>mdx</i> hearts
CARDIOVASCULAR RESEARCH
2016; 112 (2): 555-567
Abstract
Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate gene expression and are involved in cardiac diseases. Notably, a number of cardiovascular disorders have been linked to alterations in epigenetic mechanisms. Here we aimed to determine the contribution of Nup153 to the epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx mice (C57BL/10ScSn-Dmd mdx /J).Nup153 was lysine-acetylated and its expression was significantly increased at protein level in mdx hearts compared with controls. Accordingly, lysine acetyl transferase (KAT) activity associated with Nup153 was higher in mdx hearts paralleling increased binding with the lysine acetylases P300/CBP-associated factor (PCAF) and p300. Interestingly, Nup153 silencing in mdx organotypic heart tissue slices caused a reduction in PCAF- and p300-specific activities. Remarkably, the level of nitric oxide (NO), which is reduced in mdx mice, was important for KAT-dependent regulation of Nup153. In fact, treatment of mdx heart tissue with an NO donor or the KAT inhibitor anacardic acid normalized Nup153 protein expression. Nup153 was recruited to chromatin and regulated the transcription of genes involved in cardiac remodelling, including the actin-binding protein nexilin. Accordingly, nexilin protein expression was abrogated by Nup153 silencing in mdx organotypic cultures. Electrophysiological and molecular experiments revealed that Nup153 overexpression in normal cardiomyocytes increases Ca v 1.2 calcium channel expression and function. Alterations in Nup153 protein expression and intracellular localization were also found in dystrophic cardiomyocytes derived from patient-specific induced pluripotent stem cells. Importantly, Nup153 up-regulation and increased acetylation were also found in the heart of Duchenne muscular dystrophy patients.Our data indicate that Nup153 is an epigenetic regulator which, upon altered NO signalling, mediates the activation of genes potentially associated with early dystrophic cardiac remodelling.
View details for DOI 10.1093/cvr/cvw204
View details for Web of Science ID 000387985300005
View details for PubMedID 28513807
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Role of right ventricular three-dimensional electroanatomic voltage mapping for arrhythmic risk stratification of patients with corrected tetralogy of Fallot or other congenital heart disease involving the right ventricular outflow tract
INTERNATIONAL JOURNAL OF CARDIOLOGY
2016; 222: 422-429
Abstract
The post-surgical history of repaired congenital heart disease (rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden death. Electrical myocardial abnormalities could be a substrate for malignant ventricular arrhythmias.146 patients with TOF or other rCHD involving a subpulmonary right ventricle, considered to be at high arrhythmic risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM). Maps showed endocardial scars (<0.5mV) in all cases, mainly involving the RV outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved. Total scar extension, expressed as % of total endocardial area, was significantly higher in patients with QRS ≥180ms [4.5% (±2.5) vs 2.8% (±2.4), p=0.014], left and right ventricular systolic dysfunction [4.5% (±3.2) vs 2.8% (±2.3), p=0.016 and 3.5% (±3.0) vs 2.6% (±1.9), p=0.03, respectively], premature ventricular contractions (PVCs) [3.2% (±2.6) vs 2.2% (±1.8), p<0.05], exercise-induced PVCs [3.8% (±2.4) vs 2.6% (±2.2), p=0.01], previous shunt [4.0% (±2.7) vs 2.6% (±2.2), p=0.01] and reintervention [4.2% (±3.2) vs 2.6% (±2.0), p=0.008]. Scar size also showed a positive correlation with duration of post-surgical follow-up (ρ=0.01), age at correction (ρ=0.01) and absolute QRS duration (ρ=0.05).Patients with rCHD involving the right ventricle show electrical scars with variable distribution, not necessarily matching with sites of surgical lesions. Scar extension correlates with some of the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS. Thus EVM could be considered an additional tool in the assessment of risk stratification in this particular population.
View details for DOI 10.1016/j.ijcard.2016.07.231
View details for Web of Science ID 000384698300078
View details for PubMedID 27505328
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ECLS in Pediatric Cardiac Patients
FRONTIERS IN PEDIATRICS
2016; 4: 109
Abstract
Extracorporeal life support (ECLS) is an important device in the management of children with severe refractory cardiac and or pulmonary failure. Actually, two forms of ECLS are available for neonates and children: extracorporeal membrane oxygenation (ECMO) and use of a ventricular assist device (VAD). Both these techniques have their own advantages and disadvantages. The intra-aortic balloon pump is another ECLS device that has been successfully used in larger children, adolescents, and adults, but has found limited applicability in smaller children. In this review, we will present the "state of art" of ECMO in neonate and children with heart failure. ECMO is commonly used in a variety of settings to provide support to critically ill patients with cardiac disease. However, a strict selection of patients and timing of intervention should be performed to avoid the increase in mortality and morbidity of these patients. Therefore, every attempt should be done to start ECLS "urgently" rather than "emergently," before the presence of dysfunction of end organs or circulatory collapse. Even though exciting progress is being made in the development of VADs for long-term mechanical support in children, ECMO remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation. With the increase in familiarity with ECMO, new indications have been added, such as extracorporeal cardiopulmonary resuscitation (ECPR). The literature supporting ECPR is increasing in children. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS have reduced in the last 5 years and many centers support patients with functionally univentricular circulations. Improved results have been recently achieved in this complex subset of patients.
View details for DOI 10.3389/fped.2016.00109
View details for Web of Science ID 000385053100001
View details for PubMedID 27774445
View details for PubMedCentralID PMC5053996
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Modified Warden procedure in adult with partial anomalous pulmonary venous connection after previous atrial septal defect repair
COR ET VASA
2016; 58 (5): E501-E504
View details for DOI 10.1016/j.crvasa.2015.08.004
View details for Web of Science ID 000410027900011
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Duchenne Muscular Dystrophy Myogenic Cells from Urine-Derived Stem Cells Recapitulate the Dystrophin Genotype and Phenotype
HUMAN GENE THERAPY
2016; 27 (10): 772-783
Abstract
A ready source of autologous myogenic cells is of vital importance for drug screening and functional genetic studies in Duchenne muscular dystrophy (DMD), a rare disease caused by a variety of dystrophin gene mutations. As stem cells (SCs) can be easily and noninvasively obtained from urine specimens, we set out to determine whether they could be myogenically induced and useful in DMD research. To this end, we isolated stem cells from the urine of two healthy donors and from one patient with DMD, and performed surface marker characterization, myogenic differentiation (MyoD), and then transfection with antisense oligoribonucleotides to test for exon skipping and protein restoration. We demonstrated that native urine-derived stem cells express the full-length dystrophin transcript, and that the dystrophin mutation was retained in the cells of the patient with DMD, although the dystrophin protein was detected solely in control cells after myogenic transformation according to the phenotype. Notably, we also showed that treatment with antisense oligoribonucleotide against dystrophin exon 44 induced skipping in both native and MyoD-transformed urine-derived stem cells in DMD, with a therapeutic transcript-reframing effect, as well as visible protein restoration in the latter. Hence MyoD-transformed cells may be a good myogenic model for studying dystrophin gene expression, and native urine stem cells could be used to study the dystrophin transcript, and both diagnostic procedures and splicing modulation therapies in both patients and control subjects, without invasive and costly collection methods. New, bankable bioproducts from urine stem cells, useful for prescreening studies and therapeutic applications alike, are also foreseeable after further, more in-depth characterization.
View details for DOI 10.1089/hum.2016.079
View details for Web of Science ID 000384462600006
View details for PubMedID 27530229
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Isolation and characterization of human urinary stem cells from healthy donors and DMD patients as in vitro cell model for functional studies and drug testing
PERGAMON-ELSEVIER SCIENCE LTD. 2016: S158
View details for DOI 10.1016/j.nmd.2016.06.262
View details for Web of Science ID 000384790100251
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Acute Biventricular Interaction in Pediatric Patients Implanted with Continuous Flow and Pulsatile Flow LVAD: A Simulation Study
ASAIO JOURNAL
2016; 62 (5): 591-599
Abstract
Left ventricular assist devices (LVADs) are used to bridge pediatric patients till transplantation. However, the LVADs effects on right ventricular (RV) function are controversial. This work aims at studying the ventricular interdependency in the presence of continuous (c-) and pulsatile (p-) flow LVAD in pediatric patients using a lumped parameter model including the representation of the septum. Five pediatric patients' data were used to simulate patients' baseline. The effects on LV and RV functions, energetics, preloads and afterloads of different c-LVAD speeds, p-LVAD rate, p-LVAD systole duration, p-LVAD filling and ejection pressures were simulated. c-LVAD and p-LVAD unload the LV decreasing the LV external work and improving the LV ventriculo-arterial coupling and these effects are more evident increasing the c-LVAD speed and the p-LVAD rate. Continuous-LVAD and p-LVAD decrease the RV afterload, increase the RV ejection fraction and improve the RV ventriculo-arterial coupling. The changes in RV function are inversely proportional to the degree of the interventricular septum leftward shift that increased by increasing the LVAD contribution. The study of the interventricular interaction could lead to the development of a dedicated algorithm to optimize LVAD setting in pediatric population.
View details for DOI 10.1097/MAT.0000000000000396
View details for Web of Science ID 000387874900017
View details for PubMedID 27258223
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Berlin Heart EXCOR Ventricular Assist Device: Multilayer Membrane Rupture in a Pediatric Patient
ANNALS OF THORACIC SURGERY
2016; 102 (2): E129-E130
Abstract
A 2-year-old child was implanted with an Berlin Heart EXCOR Ventricular Assist Device (Berlin Heart, Berlin, Germany) as a bridge to heart transplantation for idiopathic dilated cardiomyopathy. At postoperative day 296, a significant reduction of membrane movement was observed. The device was explanted and tested on a hydronumerical circulation simulator. Findings suggested that the integrity of the multilayered membrane had been compromised. This was confirmed by a computed tomography scan of the device. The computed tomography evidenced a detachment of the 3-layered membrane, with a thinner, convex layer on the side of the air chamber and an opposite convexity of the remaining membranes. These showed an additional air space within the layers.
View details for DOI 10.1016/j.athoracsur.2016.01.022
View details for Web of Science ID 000380748600015
View details for PubMedID 27449447
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The use of a numerical model to simulate the cavo-pulmonary assistance in Fontan circulation: a preliminary verification
JOURNAL OF ARTIFICIAL ORGANS
2016; 19 (2): 105-113
Abstract
The lack of an established experience on the use of VAD for the cavo-pulmonary assistance leads to the need of dedicated VADs development and animal experiments. A dedicated numerical model could support clinical and experimental strategies design and new VADs testing. The aim of this work is to perform a preliminary verification of a lumped parameter model of the cardiovascular system to simulate Fontan physiology and the effect of cavo-pulmonary assistance. Literature data of 4 pigs were used to simulate animals' baseline, and then the model was tested in simulating Fontan circulation and cavo-pulmonary-assisted condition comparing the simulation outcome (Sim) with measured literature data (Me). The results show that the numerical model can well reproduce experimental data in all three conditions (baseline, Fontan and assisted Fontan) [cardiac output (l/min): Me = 2.8 ± 1.7, Sim = 2.8 ± 1.8; ejection fraction (%): Me = 57 ± 17, Sim = 54 ± 17; arterial systemic pressure (mmHg): Me = 41.8 ± 18.6, Sim = 43.8 ± 18.1; pulmonary arterial pressure (mmHg): Me = 15.4 ± 8.9, Sim = 17.7 ± 9.9; caval pressure (mmHg): Me = 6.8 ± 4.1, Sim = 7 ± 4.6]. Systolic elastance, arterial systemic and arterial pulmonary resistances increase (10, 69, and 100 %) passing from the biventricular circulation to the Fontan physiology and then decrease (21, 39, and 50 %) once the VAD was implanted. The ventricular external work decreases (71 %) passing from the biventricular circulation to the Fontan physiology and it increases three times after the VAD implantation in parallel with the VAD power consumption. A numerical model could support clinicians in an innovative and challenging field as the use of VAD to assist the Fontan physiology and it could be helpful to personalize the VAD insertion on the base of ventricular systo-diastolic function, circulatory parameters and energetic variables.
View details for DOI 10.1007/s10047-015-0874-5
View details for Web of Science ID 000382730900001
View details for PubMedID 26545595
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Use of Ventricular Assist Device in Univentricular Physiology: The Role of Lumped Parameter Models
WILEY-BLACKWELL. 2016: 444-453
Abstract
Failing single-ventricle (SV) patients might benefit from ventricular assist devices (VADs) as a bridge to heart transplantation. Considering the complex physiopathology of SV patients and the lack of established experience, the aim of this work was to realize and test a lumped parameter model of the cardiovascular system, able to simulate SV hemodynamics and VAD implantation effects. Data of 30 SV patients (10 Norwood, 10 Glenn, and 10 Fontan) were retrospectively collected and used to simulate patients' baseline. Then, the effects of VAD implantation were simulated. Additionally, both the effects of ventricular assistance and cavopulmonary assistance were simulated in different pathologic conditions on Fontan patients, including systolic dysfunction, diastolic dysfunction, and pulmonary vascular resistance increment. The model can reproduce patients' baseline well. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output (CO) in all the three palliation conditions (Norwood 77.2%, Glenn 38.6%, and Fontan 17.2%); (ii) decreases the SV external work (SVEW) (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) increases the mean pulmonary arterial pressure (Pap) (Norwood 39.7%, Glenn 12.1%, and Fontan 3%). In Fontan circulation, with systolic dysfunction, the left VAD (LVAD) increases CO (35%), while the right VAD (RVAD) determines a decrement of inferior vena cava pressure (Pvci) (39%) with 34% increment of CO. With diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci. With pulmonary vascular resistance increment, the RVAD allows the highest CO (50%) increment with the highest decrement of Pvci (53%). The single ventricular external work (SVEW) increases (decreases) increasing the VAD speed in cavopulmonary (ventricular) assistance. Numeric models could be helpful in this challenging and innovative field to support patients and VAD selection to optimize the clinical outcome and personalize the therapy.
View details for DOI 10.1111/aor.12583
View details for Web of Science ID 000378542800010
View details for PubMedID 26494529
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Jarvik 2000 in Pediatrics as a Bridge to Trasplantation or as Destination Therapy: Perioperative Management
ELSEVIER SCIENCE INC. 2016: S353-S354
View details for DOI 10.1016/j.healun.2016.01.1015
View details for Web of Science ID 000374718101337
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Mechanically Assisted Total Cavopulmonary Connection With an Axial Flow Pump: Computational and In Vivo Study
WILEY-BLACKWELL. 2016: 43-49
Abstract
A relevant number of patients undergoing total cavopulmonary connection (TCPC) experience heart failure (HF). Heart transplant is then the final option when all other treatments fail. The axial flow blood pumps are now the state of the art; however, there is little experience in low-pressure circuits, such as support of the right ventricle or even a TCPC circulation. A new T-shaped model of mechanically assisted TCPC using the "Jarvik Child 2000" axial pump, (flow rates between 1 and 3 L/m in a range of 5000-9000 rpm) was designed, simulated numerically, and then tested in animals. Eight sheep (42-45 kg) were studied: two pilot studies, four pump-supported (PS) TCPC for 3 h, and two not pump-supported (NPS) TCPC. In the PS, the axial pump was set to maintain the baseline cardiac output (CO). Pressures, CO, systemic and pulmonary vascular resistance, lactate levels, and blood gases were recorded for 3 h. Computational fluid dynamics (CFD) study allows us to set the feasible operating condition and the safety margins to minimize the venous collapse risk. In the NPS animals, a circulatory deterioration, with increasing lactate level, occurred rapidly. In the PS animals, there was a stable cardiac index of 2.7 ± 1.4 L/min/m(2), central venous pressure of 12.3 ± 1 mm Hg, and a mean pulmonary artery pressure (PAP) of 18.1 ± 6 after 3 h of support up to 9000 rpm. systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), blood gasses, and arterial lactate levels remained stable to baseline values. No caval collapse occurred. A new pediatric axial flow pump provides normal CO and physiologic stability in a new T-shaped model of TCPC in sheep, in vivo. CFD and in vivo data showed that this experimental arrangement will allow us to evaluate the potential for mechanical support in patients with Fontan failure avoiding major adverse events.
View details for DOI 10.1111/aor.12641
View details for Web of Science ID 000372335800008
View details for PubMedID 26777148
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Hemodynamic Effects of Ventricular Assist Device Implantation on Norwood, Glenn, and Fontan Circulation: A Simulation Study
WILEY-BLACKWELL. 2016: 34-42
Abstract
The growing population of failing single-ventricle (SV) patients might benefit from ventricular assist device (VAD) support as a bridge to heart transplantation. However, the documented experience is limited to isolated case reports. Considering the complex and different physiopathology of Norwood, Glenn, and Fontan patients and the lack of established experience, the aim of this work is to realize and test a lumped parameter model of the cardiovascular system able to simulate SV hemodynamics and VAD implantation effects to support clinical decision. Hemodynamic and echocardiographic data of 30 SV patients (10 Norwood, 10 Glenn, and 10 Fontan) were retrospectively collected and used to simulate patients' baseline. Then, the effects of VAD implantation were simulated. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output and the mean arterial systemic pressure in all the three palliation conditions (Norwood 77.2 and 19.7%, Glenn 38.6 and 32.2%, and Fontan 17.2 and 14.2%); (ii) decreases the SV external work (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) decreases the pressure pulsatility index (Norwood 65.2%, Glenn 81.3%, and Fontan 64.8%); (iv) increases the pulmonary arterial pressure in particular in the Norwood circulation (Norwood 39.7%, Glenn 12.1% and Fontan 3%); and (v) decreases the atrial pressure (Norwood 2%, Glenn 10.6%, and Fontan 8.6%). Finally, the VAD work is lower in the Norwood circulation (30.4 mL·mm Hg) in comparison with Fontan (40.3 mL·mm Hg) and to Glenn (64.5 mL·mm Hg) circulations. The use of VAD in SV physiology could be helpful to bridge patients to heart transplantations by increasing the CO and unloading the SV with a decrement of the atrial pressure and the SV external work. The regulation of the pulmonary flow is challenging because the Pap is increased by the presence of VAD. The hemodynamic changes are different in the different SV palliation step. The use of numerical models could be helpful to support patient and VAD selection to optimize the clinical outcome.
View details for DOI 10.1111/aor.12591
View details for Web of Science ID 000372335800007
View details for PubMedID 26526959
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Simulation of acute haemodynamic outcomes of the surgical strategies for the right ventricular failure treatment in pediatric LVAD
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
2015; 38 (12): 638-645
Abstract
Right ventricular failure (RVF) is one of the major complications during LVAD. Apart from drug therapy, the most reliable option is the implantation of RVAD. However, BIVAD have a poor prognosis and increased complications. Experiments have been conducted on alternative approaches, such as the creation of an atrial septal defect (ASD), a cavo-aortic shunt (CAS) including the LVAD and a cavo-pulmonary connection (CPC). This work aims at realizing a lumped parameter model (LPM) to compare the acute hemodynamic effects of ASD, CPC, CAS, RVAD in LVAD pediatric patients with RVF.Data of 5 pediatric patients undergoing LVAD were retrospectively collected to reproduce patients baseline hemodynamics with the LPM. The effects of continuous flow LVAD implantation complicated by RVF was simulated and then the effects of ASD, CPC, CAS and RVAD treatments were simulated for each patient.The model successfully reproduced patients' baseline and the hemodynamic effects of the surgical strategies. Simulating the different surgical strategies, an unloading of the right ventricle and an increment of left ventricular preload were observed with an improvement of the hemodynamics (total cardiac output: ASD +15%, CPC +10%, CAS +70% RVAD +20%; right ventricular external work: ASD -19%, CPC -46%, CAS -76%, RVAD -32%; left ventricular external work: ASD +12%, CPC +28%, RVAD +64%).The use of numerical model could offer an additional support for clinical decision-making, also potentially reducing animal experiments, to compare the outcome of different surgical strategies to treat RVF in LVAD.
View details for DOI 10.5301/ijao.5000462
View details for Web of Science ID 000371790500003
View details for PubMedID 26847500
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Extracorporeal membrane oxygenation as a bridge to allogeneic T-cell depleted hematopoietic stem cell transplantation in infants with severe combined immune deficiency: is it feasible?
INTENSIVE CARE MEDICINE
2014; 40 (10): 1600-1601
View details for DOI 10.1007/s00134-014-3432-3
View details for Web of Science ID 000342433000034
View details for PubMedID 25112503
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Extracorporeal membrane oxygenation in pediatric recipients of hematopoietic stem cell transplantation: an updated analysis of the Extracorporeal Life Support Organization experience
INTENSIVE CARE MEDICINE
2014; 40 (5): 754-756
View details for DOI 10.1007/s00134-014-3240-9
View details for Web of Science ID 000335662400020
View details for PubMedID 24556913
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Adoptive Immunotherapy With Antigen-Specific T Cells During Extracorporeal Membrane Oxygenation (ECMO) for Adenovirus-Related Respiratory Failure in a Child Given Haploidentical Stem Cell Transplantation
PEDIATRIC BLOOD & CANCER
2014; 61 (2): 376-379
Abstract
We report on the successful infusion of human adenovirus (HAdV)-specific T cells in a child with congenital amegakaryocytic thrombocytopenia, given T-cell-depleted hematopoietic stem cell transplantation (HSCT) from the HLA-haploidentical mother during extracorporeal membrane oxygenation (ECMO) for severe HAdV-related respiratory failure. Donor-derived, interferon (IFN)-γ-secreting HAdV-specific T cells were enriched using the cytokine capture assay, after in vitro stimulation with overlapping peptides from the immunodominant HAdV5 hexon protein. Two weeks after T-cell transfer, viral load decreased and ECMO was discontinued. T-cell responses to HAdV antigens were documented after four weeks and were associated with viral clearance, immune reconstitution and clinical amelioration.
View details for DOI 10.1002/pbc.24753
View details for Web of Science ID 000328694300043
View details for PubMedID 24039155