Cardiomyocyte hyperplasia and immaturity but not hypertrophy are characteristic features of patients with RASopathies.

AIMS: RASopathies are caused by mutations in genes that alter the MAP kinase pathway and are marked by several malformations with cardiovascular disorders as the predominant cause of mortality. Mechanistic insights in the underlying pathogenesis in affected cardiac tissue are rare. The aim of the study was to assess the impact of RASopathy causing mutations on the human heart. METHODS AND RESULTS: Using single cell approaches and histopathology we analyzed cardiac tissue from children with different RASopathy-associated mutations compared to age-matched dilated cardiomyopathy (DCM) and control hearts. The volume of cardiomyocytes was reduced in RASopathy conditions compared to controls and DCM patients, and the estimated number of cardiomyocytes per heart was ∼4-10 times higher. Single nuclei RNA sequencing of a 13-year-old RASopathy patient (carrying a PTPN11 c.1528C > G mutation) revealed that myocardial cell composition and transcriptional patterns were similar to <1 year old DCM hearts. Additionally, immaturity of cardiomyocytes is shown by an increased MYH6/MYH7 expression ratio and reduced expression of genes associated with fatty acid metabolism. In the patient with the PTPN11 mutation activation of the MAP kinase pathway was not evident in cardiomyocytes, whereas increased phosphorylation of PDK1 and its downstream kinase Akt was detected. CONCLUSION: In conclusion, an immature cardiomyocyte differentiation status appears to be preserved in juvenile RASopathy patients. The increased mass of the heart in such patients is due to an increase in cardiomyocyte number (hyperplasia) but not an enlargement of individual cardiomyocytes (hypertrophy).

Hypoplastic Left Heart Syndrome Palliation: Technical Aspects and Common Pitfalls of the Hybrid Approach.

The Giessen hybrid strategy is used for initial palliation of HLHS and variants when the intent is to pursue further staged palliative reconstruction toward Fontan circulation. It is also used for initial palliation of HLHC and other anomalies with potential for eventual biventricular repair. From June 1998 - October 2021, 197 patients with HLHS and related variants underwent hybrid stage 1. Follow-up is complete (median 8.3 [range 0-23.3] years). Operative mortality for hybrid stage I was 3.6% (7/197); reduced to 2.8% since 2010 (4/141). Interstage mortality was 4.1% (8/197). Operative mortality for comprehensive stage II was 5.8% (10/172), and since 2010 was 1.8% (2/113 patients). Fontan completion has been accomplished in 117 patients, and 33 are still awaiting stage III. Twelve patients underwent heart transplantation. Over 23 years, overall survival is 77.7% and transplant-free survival is 73.6%.

Hypoplastic Left Ventricle: Left Ventricular Recruitment With Hybrid Approach.

Decision-making for biventricular repair (BVR) or univentricular palliation is challenging in neonates with hypoplastic left heart complex (HLHC). Hybrid strategy can be used successfully to achieve BVR in some of these patients. Between June 1998 and January 2022, 342 patients with a diagnosis of HLHS/variants, ductal-dependent lower body circulation with two ventricles, or HLHC with borderline left ventricle (LV) underwent initial bilateral pulmonary artery banding and ductal stenting in our institution. Among these 342 patients, 224 patients were defined as HLHS/variants and underwent univentricular palliation. 118 patients were determined to have borderline LV and hypoplastic left ventricular structures (HLHC, n = 48) or ductal-dependent lower body circulation with two ventricles (n = 70) considered suitable for BVR. 48 patients had multilevel obstructions including both aortic and mitral valve hypoplasia, aortic arch hypoplasia, and borderline LV. These were considered to have HLHC. These 48 HLHC patients are the subject of this report. Neonatal hybrid palliation at a median age of seven days was performed in 48 patients and 46 patients underwent BVR at a median age of 156 days. In 46 patients who underwent BVR, hospital mortality was not observed. The median follow-up was 66 months, with no late mortality. Heart transplant-free survival at 5, 10, and 15 years was 95.7%. 12 patients (26%) required reoperation and 9 (19.5%) required catheter reinterventions. Hybrid palliation may increase the chances for biventricular circulation in patients with borderline LV and small left-sided structures. Giessen hybrid approach as a left ventricular recruitment strategy achieves excellent early and long-term results.

Effects of pulmonary artery banding in doxorubicin-induced left ventricular cardiomyopathy.

OBJECTIVE: Central pulmonary banding has been proposed as a novel alternative for the treatment of left ventricular dilated cardiomyopathy in children. We sought to investigate the effects of central pulmonary banding in an experimental model of doxorubicin-induced left ventricular dilated cardiomyopathy. METHODS: Four-month-old sheep (n = 28) were treated with intermittent intracoronary injections of doxorubicin (0.75 mg/kg/dose) into the left main coronary artery. A total dose of up to 2.15 mg/kg of doxorubicin was administered until signs of left ventricular dilation with functional impairment occurred by transthoracic echocardiography evaluation. Animals that survived were treated with surgical central pulmonary banding through a left anterior thoracotomy or sham surgery. Transthoracic echocardiography and pressure-volume loop measurements were used to compare left ventricular function preoperatively and 3 months later. Macroscopic and microscopic histologic examinations followed after hearts were harvested. RESULTS: Nine animals from the central pulmonary banding group and 8 animals from the sham group survived and were included in the final analysis. Both groups showed similar inflammation and fibrosis upon histologic examination consistent with the toxic myocardial effects of doxorubicin. There were no differences in the echocardiographic measurements before central pulmonary banding or sham operation. Baseline measurements before the central pulmonary banding/sham operation were considered as 100%. The central pulmonary banding group had better left ventricular ejection fraction (102.5% ± 21.6% vs 76.7% ± 11.7%, P = .01), with a tendency for smaller left ventricular end-diastolic (101.2% ± 7.4% vs 120.4% ± 10.8%, P = .18) and significantly smaller end-systolic (100.3% ± 12.9% vs 116.5 ± 9.6%, P = .02) diameter of the left ventricle in comparison with the sham animals at 3 months. The end-systolic volume (101.4% ± 31.6% vs 143.4% ± 28.6%, P = .02) was significantly lower in the central pulmonary banding group 3 months postoperatively. Fractional shortening in the long axis (118.5% ± 21.5% vs 85.2% ± 22.8%, P = .016) and short axis (122.5% ± 18% vs 80.9% ± 13.6%, P = .0005) revealed significantly higher values in the central pulmonary banding group. In the conductance catheter measurements, no significant differences were seen between the groups for the parameters of systolic and diastolic function. CONCLUSIONS: Central pulmonary artery banding in the setting of experimental toxic left ventricular dilated cardiomyopathy improved left ventricular echocardiographic function and dimensions.

Giessen Procedure as Comprehensive Stage II Palliation With Aortic Arch Reconstruction After Hybrid Bilateral Pulmonary Artery Banding and Ductal Stenting for Hypoplastic Left Heart Syndrome.

This article reviews our experience using hybrid stage I palliation in the neonatal period and subsequently with comprehensive stage II palliation for hypoplastic left heart syndrome. Between June 1998 and April 2017, 154 patients with the diagnosis of hypoplastic left heart syndrome and variants underwent a hybrid stage I palliation (bilateral pulmonary artery banding and ductal stenting). One hundred thirty-nine patients could be further univentricularly palliated. One hundred twenty-one patients underwent a comprehensive stage II operation with an operative mortality of 6.6%. The hybrid procedure provides reproducible results with reduced in-hospital, interstage, and long-term mortality and lower rates of aortic arch reinterventions.

Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?

OBJECTIVE: This retrospective study presents our operative results, mortality, and morbidity with regard to pulmonary artery growth and reinterventions on the pulmonary artery and aortic arch, including key features of our institutional standards for the 3-stage hybrid palliation of patients with hypoplastic left heart syndrome. METHODS: Between June 1998 and February 2015, 182 patients with hypoplastic left heart structures underwent the Giessen hybrid stage I procedure. Among these, 126 patients with hypoplastic left heart syndrome who received a univentricular palliation or heart transplantation were included in the main analysis. Median age and body weight of patients at hybrid stage I were 6 days (0-237) and 3.2 kg (1.2-7), respectively. Comprehensive stage II operation was performed at 4.5 months (2.9-39.5), and Fontan completion was established at 33.7 months (21.1-108.2). Operative and interstage mortality, morbidity, growth and reinterventions on the pulmonary arteries, and long-term operative results of the aortic arch reconstruction were assessed. RESULTS: Median follow-up time after Giessen hybrid stage I palliation was 4.6 years (0-16.8). Operative mortality at hybrid stage I, comprehensive stage II, and Fontan completion was 2.5%, 4.9%, and 0%, respectively. Cumulative interstage mortality was 14.2%. At 10 years, the probability of survival is 77.8%. Body weight (<2.5 kg) and aortic atresia had no significant impact on survival. McGoon ratio did not differ at comprehensive stage II and Fontan completion (P = .991). Freedom from pulmonary artery intervention was estimated to be 32.2% at 10 years. Aortic arch reinterventions were needed in 16.7% of patients; 2 reoperations on the aortic arch were necessary. CONCLUSIONS: In view of the early results and long-term outcome, the hybrid approach has become an alternative to the conventional strategy to treat neonates with hypoplastic left heart syndrome and variants. Further refinements are warranted to decrease patient morbidity.

Evaluación diagnóstica y tratamiento de pacientes con hematoma de la vaina de los rectos / Diagnostic evaluation and treatment of patients with rectus abdominis hematoma

OBJETIVO: Identificar las características clínicas, las modalidades de tratamiento y la evolución del hematoma espontáneo de la vaina del recto (HEVR). En la literatura, no hay ningún estudio clínico prospectivo sobre el tratamiento en un ámbito de investigación clínica. MÉTODOS: Se incluyeron en el estudio 17 pacientes con HEVR que fueron diagnosticados y tratados entre marzo de 2012 y marzo de 2014 en el Departamento de Cirugía General del Hospital Docente e Investigador de la Universidad de Erzincan. Se evaluaron los datos de edad, sexo, peso, altura, factores predisponentes, comorbilidades, índice de Charlson, tratamiento médico actual, signos a la exploración física, exploraciones de diagnóstico por la imagen, valor mínimo de la hemoglobina, tipo sanguíneo, tipo de HEVR, valores de INR/mutación de factor V Leiden/factor VII/factor VIII/factor X/proteína S/proteína C, método de tratamiento, transfusiones, duración de la hospitalización y evolución clínica. RESULTADOS: Trece pacientes fueron mujeres. La media de edad fue de 63,3 ± 18,7 años (rango, 22-87 años), y la media del IMC fue de 27,8 ± 3,5 (rango, 20,9-33,7). Seis pacientes presentaban un HEVR de grado I, 5 un HEVR de grado II y 6 un HEVR de grado III. Trece fueron ingresados durante un periodo medio de hospitalización de 9,3 ± 8,1 días (rango, 1-30 días). La tasa de mortalidad atribuible al HEVR fue del 5,8%. CONCLUSIONES: Un diagnóstico precoz del HEVR mediante ecografía y/o tomografía computarizada es importante para obtener una tasa de mortalidad baja. A pesar de que los tratamientos médicos son importantes, pueden ser necesarias una embolización arterial mediante radiología intervencionista o intervenciones más radicales como la cirugía

PURPOSE: To identify clinical characteristics, treatment modalities, and course of spontaneous rectus sheath hematoma (SRSH). In the literature, there is no prospective clinical trial that is intended for treatment in clinical research. METHODS: Seventeen SRSH patients diagnosed and treated between March 2012 and March Hospital were included. Age, sex, weight, height, predisposing factors, comorbid diseases, Charlson index, current medical treatment, physical examination signs, imaging methods, lowest hemoglobin value, blood type, SRSH type, INR/Factor V Leiden mutation/Factor VII/ Factor VIII/Factor X/Protein S/Protein C values, treatment method, transfusions hospitalization duration, and outcome were studied. RESULTS: Thirteen patients were female. The mean age was 63.3 ± 18.7 years (range, 22-87 years), and the mean BMI was 27.8 ± 3.5 (range, 20.9-33.7). Six patients had Grade I SRSH, 5 had Grade II SRSH, and 6 had Grade III SRSH. Thirteen were hospitalized for a mean duration of 9.3 ± 8.1 days (range, 1-30 days). The death rate attributable to SRSH was 5.8%. CONCLUSION: Early diagnosis of SRSH by ultrasonography and/or computerized tomography is important for a low mortality rate. Even though medical treatments are important, arterial embolization by interventional radiology, or more radical interventions such as surgery, may be required

Diagnostic evaluation and treatment of patients with rectus abdominis hematoma.

PURPOSE: To identify clinical characteristics, treatment modalities, and course of spontaneous rectus sheath hematoma (SRSH). In the literature, there is no prospective clinical trial that is intended for treatment in clinical research. METHODS: Seventeen SRSH patients diagnosed and treated between March 2012 and March 2014 at the general Surgery Department of Erzincan University Training and Research Hospital were included. Age, sex, weight, height, predisposing factors, comorbid diseases, Charlson index, current medical treatment, physical examination signs, imaging methods, lowest hemoglobin value, blood type, SRSH type, INR/Factor V Leiden mutation/Factor VII/Factor VIII/Factor X/Protein S/Protein C values, treatment method, transfusions hospitalization duration, and outcome were studied. RESULTS: Thirteen patients were female. The mean age was 63.3 ± 18.7 years (range, 22-87 years), and the mean BMI was 27.8 ± 3.5 (range, 20.9-33.7). Six patients had Grade I SRSH, 5 had Grade II SRSH, and 6 had Grade III SRSH. Thirteen were hospitalized for a mean duration of 9.3 ± 8.1 days (range, 1-30 days). The death rate attributable to SRSH was 5.8%. CONCLUSION: Early diagnosis of SRSH by ultrasonography and/or computerized tomography is important for a low mortality rate. Even though medical treatments are important, arterial embolization by interventional radiology, or more radical interventions such as surgery, may be required.

Coronary artery fistula between left coronary artery and coronary sinus in newborn.

Aneurysmal circumflex coronary artery fistula connected to the coronary sinus is a rare clinical entity that usually remains asymptomatic until later in life. The timing of surgical treatment for asymptomatic patients is crucial. The decision to leave or exclude the aneurysmatic coronary artery following ligation of the fistula is controversial. Herein, we report the successful management of a coronary fistula between the circumflex artery and the coronary sinus without using cardiopulmonary bypass during the newborn period.

Early initiation of peritoneal dialysis after arterial switch operations in newborn patients.

BACKGROUND AND AIM: We investigated the clinical outcome of early initiated peritoneal dialysis (PD) use in our newborn patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA) and had routine intraoperative PD catheter implantation. We determined the risk factors for PD, factors associated with prolonged PD, morbidity, and mortality. The aim of the present study was to describe our experience of using PD in this patient cohort. MATERIALS AND METHODS: Eighty two patients who were diagnosed with TGA and TGA-ventricular septal defect (VSD) and who had undergone TGA correction operation in Baskent University, Istanbul Medical Research and Training Hospital between 2007 and 2012 were retrospectively investigated. All the patients were under 30 days old. PD catheters were routinely implanted intraoperatively at the end of the operation. PD was initiated in transient renal insufficiency. In the absence of oliguria and increased creatinine level, PD was established in the presence of one of the following: clinical signs of fluid overload, hyperkalemia (>5 mEq/L), persistent metabolic acidosis, lactate level above 8 mmol/L or low cardiac output syndrome. The patients were divided into two groups according to the need for postoperative PD (PD group and non-PD group). PD was initiated in 32 (39%) patients after the operation, whereas 50 (61%) patients did not need dialysis. The clinical outcomes and perioperative data of the two groups were compared. RESULTS: The demographics in the two groups were similar. Cardiopulmonary bypass time was longer in the PD group [non-PD group, 175.24 ± 32.39 min; PD group, 196.22 ± 44.04 min (p < 0.05)]. Coronary anomaly was found to be higher in the PD group [non-PD group, n = 2 patients (4.0%); PD group, n = 7 patients (21.9%); p < 0.05]. There was more need for PD in TGA + VSD patients [simple TGA patients, n = 14; TGA + VSD patients, n = 18 (p < 0.05)]. PD rate was higher in patients whose sterna were left open at the end of the operation (p < 0.05). The ventilator time [non-PD group, 4.04 ± 1.51 days; PD group, 8.12 ± 5.21 days (p < 0.01)], intensive care unit stay time [non-PD group, 7.98 ± 5.80 days; PD group, 15.93 ± 18.31 days (p < 0.01)], and hospital stay time were significantly longer in the PD group [non-PD group, 14.98 ± 10.14 days; PD group, 22.84 ± 20.87 days (p < 0.01)]. CONCLUSION: We advocate routine implantation of PD catheters to patients with TGA-VSD, coronary artery anomaly, and open sternum in which we have determined high rate of postoperative PD need.

Delayed sternal closure after pediatric cardiac operations; single center experience: a retrospective study.

BACKGROUND: Delayed sternal closure (DSC) after cardiac surgery is a therapeutic option in the treatment of the severely impaired heart in pediatric cardiac surgery. The results with the technique of DSC over a 4-year period are examined with regard to mortality and morbidity. METHODS: We retrospectively reviewed records of 38 patients who had undergone DSC among 1100 congenital cardiac operations. Indication of DSC, time to sternal closure, pre and post closure cardiopulmonary and metabolic status, mortality, rate of wound and bloodstream infections were recorded. RESULTS: The mean sternal closure time was 2.9 days. The mortality rate was 34.2% (n = 13). Twenty (52.6%) patients required prolonged antibiotic use due to postoperative infection. There was gram negative microorganism predominance. There were 4 (10.5%) patients with postoperative mediastinitis. Postoperative infection rate statistically increased with cardiopulmonary bypass time (CPBT), sternal closure time (SCT) and intensive care unit (ICU) stay time (p = 0.039;p = 0.01;p = 0.012). On the other hand, the mortality rate significantly increased with increased cross clamp time (CCT), SCT, and extracorporeal membrane oxygenation (ECMO) use (p = 0.017; p = 0.026; p = 0.03). Single ventricular physiology was found to be risk factor for mortality in delayed sternal closure (p < 0.007). CONCLUSIONS: Elective DSC does not reduce the morbidity. The prolonged sternal closure time is associated with increased rate of postoperative infection rate; therefore early closure is strongly advocated.

[Follow-up of our patients with transposition of the great arteries and arterial switch operation; comparison of simple and complex transposition cases]. / Arteriyel "switch" ameliyati yapilan büyük arter transpozisyonlu hastalarimizin izlemi; basit ve kompleks transpozisyon olgularinin karsilastirilmasi

OBJECTIVE: 1. Follow-up data of patients with simple transposition of great arteries (TGA) and TGA with ventricular septal defect (VSD), who had arterial switch operation (ASO) are compared. 2. Factors affecting mortality and morbidity after ASO are described. METHODS: Seventy-six patients, who had an ASO between April 2007 and August 2010 were studied retrospectively. The patients with intact ventricular septum (IVS) (n=36) were in Group 1, and those with VSD (n=40) in Group 2. The pre and postoperative clinical and echocardiographic variables and intensive care unit (ICU) outcomes were compared among groups using Mann-Whitney U, Pearson correlation and logistic regression tests. RESULTS: The mean age at operation was 44.1 days, weight was 3.6±0.98 kg. Patients were followed for 15.5±11.21 months. The aortic cross-clamp (AoCC) and cardiopulmonary bypass (CPB) times were higher in patients with VSD (p=0.001, p=0.004). Patients in Group 1 had longer inotropic agent infusion (p=0.001). Length of stay in ICU was similar in two groups (p>0.05). There was no correlation between the length of stay in ICU and age, weight, CPB time, AoCC time. Aortic regurgitation was more frequent in Group 2 (p=0.02). During follow-up, 12 patients died (15.7%), and 8 patients had a revision operation (10.5%) (diaphragmatic plication in 4, pulmonary artery reconstruction in 1, recoarctation operation in 3 patients). Mortality was similar in groups (p>0.05). CONCLUSION: Arterial switch operation provides anatomical correction in TGA. Appropriate timing and good perioperative planning facilitates low morbidity and mortality in patients with VSD as in patients with simple TGA.

A rare anatomic variation: a combination of anomalous origin of the right subclavian artery from the main pulmonary artery, ventricular septal defect, and aortic coarctation.

BACKGROUND: We present a rare case of an anomalous origin of the right subclavian artery (SA) from the pulmonary artery (PA) associated with ventricular septal defect (VSD) and aortic coarctation. CASE REPORT: Critical aortic coarctation and VSD were diagnosed in a neonate, and coarctation angioplasty was successfully performed. Severe cardiac failure developed after this procedure, however, and closure of the VSD was planned. RESULTS: The anomalous SA was diagnosed during the operation when the cardiopulmonary bypass was initiated. As the pulmonary blood flow decreased, a difference in pulse pressures between the right radial artery and the ascending aorta was noticed to be due to the subclavian steal phenomenon. The difference decreased from 60 mm Hg to 25 mm Hg following ligation of the SA at its origin from the PA. The patient was discharged on the eighth postoperative day without any problems. CONCLUSION: An abnormal origin of the right SA from the main PA associated with VSD and aortic coarctation is a unique combination that, if unnoticed preoperatively, may create difficulties during the operation.