Long-term assessment of clinical outcomes and disease progression in patients with corrected Tetralogy of Fallot.

OBJECTIVE: Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. PATIENTS AND METHODS: Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspid regurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. RESULTS: Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. CONCLUSIONS:  Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.

Evolution of Ventricular Energetics in the Different Stages of Palliation of Hypoplastic Left Heart Syndrome: A Retrospective Clinical Study.

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.

Tailoring the hybrid palliation for hypoplastic left heart syndrome: A simulation study using a lumped parameter model.

The results of Hybrid procedure (HP) for the hypoplastic left heart syndrome (HLHS) depend on several variables: pulmonary artery banding tightness (PAB), atrial septal defect size (ASD) and patent ductus arteriosus stent size (PDA). A HP complication could be the aortic coarctaction (CoAo). The reverse Blalock-Taussig shunt (RevBT) placement was proposed to avoid CoAo effects. This work aims at developing a lumped parameter model (LPM) to investigate the effects of the different variables on HP haemodynamics. A preliminary verification was performed collecting measurements on a newborn HLHS patient to calculate LPM input parameters to reproduce patient's baseline. Results suggest that haemodynamics is affected by ASD (ASD: 0.15-0.55 cm, pulmonary to systemic flow ratio Qp/Qs: 0.73-1, cardiac output (CO): 1-1.5 l/min and ventricular stroke work SW: 336-577 ml mmHg) and by the PAB diameter (PAB: 0.07-0.2 cm, Qp/Qs: 0.46-2.1, CO: 1.3-1.6 l/min and SW: 591-535 ml mmHg). Haemodynamics was neither affected by RevBT diameter nor by PDA diameter higher than 0.2 cm. RevBT implantation does not change the HP haemodynamics, but it can make the CoAo effect negligible. LPM could be useful to support clinical decision in complex physiopathology and to calibrate and personalise the parameters that play a role on flow distribution.

Percutaneous treatment of abdominal coarctation in children using a covered stent.

Coarctation of the abdominal aorta is extremely rare. It generally involves a long segment of the descending aorta and causes uncontrolled and unexplainable hypertension in children. The therapeutic choice is very challenging because acute and chronic complications are reported for both the surgical and the percutaneous approaches. The two reported cases of abdominal coarctation were treated primarily and successfully through the use of covered stents. Three covered stents were implanted in two children. No complication occurred with either procedure. At this writing, an 18-month follow-up assessment has found the patients in good health with no restenosis at the coarctation site. Covered stent implantation in children with abdominal coarctation is a feasible, safe, and effective procedure. It provides adequate relief of symptoms and reduces the risk of aneurysm formation. To avoid covering important side branches with polytetrafluoroethylene, this type of procedure must be preceded by precise study of the aorta and its branches.

Syndromic non-compaction of the left ventricle: associated chromosomal anomalies.

Non-compaction of the left ventricle (NCLV) is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intertrabecular recesses. Associated extracardiac anomalies occur in 14-66% of patients of different series, while chromosomal anomalies were reported in sporadic cases. We investigated the prevalence of chromosomal imbalances in 25 syndromic patients with NCLV, using standard cytogenetic, subtelomeric fluorescent in situ hybridization, and array-comparative genomic hybridization (CGH) analyses. Standard chromosome analysis disclosed an abnormality in three (12%) patients, including a 45,X/46,XX mosaic, a 45,X/46,X,i(Y)(p11) mosaic, and a de novo Robertsonian 13;14 translocation in a child affected by hypomelanosis of Ito. Cryptic chromosome anomalies were found in six (24%) cases, including 1p36 deletion in two patients, 7p14.3p14.1 deletion, 18p subtelomeric deletion, 22q11.2 deletion associated with velo-cardio-facial syndrome, and distal 22q11.2 deletion, each in one case. These results recommend accurate clinical evaluation of patients with NCLV, and suggest that chromosome anomalies occur in about one third of syndromic NCLV individuals, without metabolic/neuromuscular disorder. Array-CGH analysis should be included in the diagnostic protocol of these patients, because different submicroscopic imbalances are causally associated with this disorder and can pinpoint candidate genes for this cardiomyopathy.

Hypertrophic cardiomyopathy and mtDNA depletion. Successful treatment with heart transplantation.

Cardiomyopathy associated with a mitochondrial DNA depletion syndrome is a rare condition. We report on a child with a hypertrophic cardiomyopathy and a mitochondrial depletion syndrome who was successfully treated by heart transplantation, given the tissue-specific nature of her mitochondrial disorder.

Heart transplantation on the first day of life from an anencephalic donor.

Heart transplantation on the first day of life, and graft harvesting from anencephalic donors, have been very rare events in the history of transplantation. At Bambino Gesù Hospital (Rome), heart transplantation was performed on a newborn 9 h after birth, using a graft harvested from an anencephalic donor. This graft achieved a good cardiocirculatory function, but the recipient died of necrotizing enterocolitis (NEC) on post-operative day (POD) 10. Despite failure, this case and other reports support the concept that hearts from anencephalic donors can work normally, and indicate that heart transplantation on the first day of life may have a favorable outcome if postoperative maintenance of multi-organ balance and function is successful.

Tachycardias in children originating in the right ventricular outflow tract: lack of clinical features predicting the presence and severity of the histopathological substrate.

The aim was to determine whether the clinical features of tachycardias originating from the right ventricular outflow tract in children with an apparently normal heart could predict the presence and the severity of the histopathological substrate. Thirteen children (median age 6 years; range 6 months-12 years) with tachycardia originating from the right ventricular outflow tract of apparently normal hearts, were assessed by echocardiography, heart catheterization with angiography, endomyocardial biopsy (13 patients) and magnetic resonance imaging (MRI) (nine patients). Tachycardia was symptomatic in six and sustained in nine. Endomyocardial biopsy and MRI revealed acute myocarditis in five patients (38%), fatty infiltration of the right ventricle in two (15%), and minor histologic abnormalities in three (23%). Myocarditis was diagnosed in three of nine patients with sustained ventricular tachycardia, as opposed to two of four with non-sustained tachycardia (p = NS); in three of six symptomatic versus two of seven asymptomatic patients (p = NS); and in two of eight patients in whom ventricular tachycardia was induced during exercise testing as opposed to one of three in which it was not inducible (p = NS). A histopathological substrate was found in six of nine patients with sustained ventricular tachycardia, and in all four with non-sustained tachycardia (p = NS); in five of six patients with symptoms versus five of seven asymptomatic patients (p = NS); and in five of eight with inducible ventricular tachycardia during exercise testing versus all three in whom it was not inducible (p = NS). The mean rate of tachycardia was 184+/-39 beats min(-1) in patients with myocarditis, as opposed to 171+/-48 in patients without myocarditis (p = NS); and 163+/-33 in patients with a histopathological substrate compared with 210+/-65 in patients without a histopathological substrate (p = NS). It is concluded that a histopathological substrate is present in the greater majority of children affected by the so-called right ventricular outflow tract tachycardia, but that the clinical features of the tachycardia do not predict the presence and the severity of this histopathological substrate.

Noonan syndrome: structural abnormalities of the mitral valve causing subaortic obstruction.

UNLABELLED: Among 41 consecutive children with classic Noonan syndrome, 27 patients (66%) presented cardiac anomalies. Eight patients (19.5%) had a congenital anomaly of the mitral valve consisting of 5 with partial atrioventricular canal defect and 3 with anomalous insertion of the mitral valve on the ventricular septum. Five patients (12%) presented with a significant left ventricular outflow tract obstruction caused by the anterior leaflet of the mitral valve: two cases with atrioventricular canal and three cases with isolated anomalous insertion of the mitral valve. Echocardiography is the best tool for the diagnosis. Cardiac defects of patients with Noonan syndrome may be explained on the basis of anomalies of the extracellular matrix involving cardiac valves including the mitral valve. CONCLUSION: In children with Noonan syndrome and left ventricular hypertrophy a careful echocardiographic assessment of the mitral valve should reveal those in whom the left ventricular outflow tract obstruction is anatomical in nature.

[Transesophageal atrial stimulation in the oral treatment of supraventricular reciprocal paroxysmal tachycardia in infants]. / La stimolazione atriale transesofagea nel trattamento orale della tachicardia parossistica reciprocante sopraventricolare del lattante.

INTRODUCTION: The aim of the study was the evaluation of the usefulness of transesophageal atrial pacing in predicting chronic oral treatment efficacy of symptomatic reciprocating supraventricular tachycardia in infants and in avoiding the risk of very dangerous recurrences at home. METHODS: We studied 13 infants (11 males, 2 females, mean age 43 +/- 31 days) with symptomatic reciprocating supraventricular tachycardia and no structural heart disease. All patients had chronic oral therapy, using the drug effective in acute i.v. somministration. Each patient was discharged when supraventricular tachycardia was not inducible with transesophageal atrial pacing after 5 half-lives of the drug used in chronic oral treatment. All patients, every 6 months, were retested with transesophageal atrial pacing alternatively during chronic oral therapy and after complete wash out. Oral therapy was stopped in each patient when supraventricular tachycardia was not inducible after the wash out. RESULTS: The number of oral treatments tested for each patient were 2 +/- 1 (range 1-5). The number of transesophageal studies performed for each patient were 4 +/- 2 (range 3-7). No patient had symptomatic episodes of supraventricular tachycardia or needed to change therapy during the follow-up. The oral treatment was stopped after the twelfth month of life in 8 patients and after the twenty-fourth in 2 others without recurrences. CONCLUSION: Transesophageal atrial pacing seems to be useful in predicting accurately and rapidly the oral treatment efficacy of supraventricular tachycardia in infants. Our protocol seems to be effective to avoid dangerous recurrences of tachycardia and to decide when we can stop therapy without risk.

Dilated cardiomyopathy caused by acute myocarditis in pediatric patients: evolution of myocardial damage in a group of potential heart transplant candidates.

Dilated cardiomyopathy, frequently caused by acute myocarditis, is a common indication for heart transplantation in pediatric patients. The prognosis of children with acute myocarditis is not well known but is believed to be poor. We report the short-term follow-up in 20 pediatric patients (mean age 22 +/- 19 months) with acute myocarditis diagnosed by endomyocardial biopsy. All patients were treated by immunosuppression (cyclosporine and steroids). Endomyocardial biopsy was repeated after 6 months in all patients and after 1 year in patients with persistent acute myocarditis. To evaluate left ventricular function, two-dimensional echocardiography was performed at the time of each endomyocardial biopsy, and left ventricular end-diastolic volume index and ejection fraction were calculated. After 6 months, endomyocardial biopsy showed persistence of acute myocarditis in 13 of 20 patients. After 1 year, endomyocardial biopsy performed in 11 of 13 patients with persistent acute myocarditis showed ongoing acute myocarditis in 10 of 11 patients. On admission to the hospital, 16 of 20 patients had left ventricular dilation (end-diastolic volume index 122 +/- 19 ml/m2; normal values 63 +/- 17 ml/m2) and 20 of 20 had decreased contractility (ejection fraction 34% +/- 11%; normal values 66.1% +/- 5.2%). After 6 months, in all patients the end-diastolic volume index decreased to 73 +/- 23 ml/m2 (p < 0.001), and the ejection fraction increased to 56% +/- 8% (p < 0.000001).(ABSTRACT TRUNCATED AT 250 WORDS)

Myopathy and hypertrophic cardiomyopathy with selective lysis of thick filaments.

We present a undescribed condition in a girl who died at 8 years of hypertrophic cardiomyopathy. Muscle and endomyocardial biopsies disclosed a selective loss of thick filaments ultrastructurally. In muscle biopsy histochemical abnormalities of myofibrillar AT-Pase were confined to type 1 fibres. Gel electrophoresis of muscle homogenate showed no qualitative abnormalities of slow and fast myosin heavy chains (MHC) and light chains, and the amount of the different myosin isozymes was in agreement with histochemical myofibrillar ATPase findings. The pathogenetic mechanisms have not been elucidated in this case but we suspect an abnormality of the beta-cardiac MHC gene, the only gene expressed in the heart and in type 1 skeletal muscle fibres.

Total extracardiac right heart bypass.

BACKGROUND: Total cavopulmonary connection has been proposed as a rational alternative to atriopulmonary connection for complex Fontan operations. In addition to fluid dynamic advantages proposed by de Leval, total right heart bypass may address an emerging important issue after repair of single ventricle: late atrial arrhythmias. The purpose of this study is to document the postoperative hemodynamic findings in 22 consecutive patients who received a total extracardiac right heart bypass with an inferior vena cava-to-pulmonary artery extracardiac Dacron conduit with a modified Glenn anastomosis (superior vena cava-to-pulmonary artery anastomosis). METHODS AND RESULTS: Twenty-eight patients with complex congenital heart disease underwent this surgical procedure. One patient died (early mortality, 3.5%). Mean follow-up was 13.9 months. Postoperative cardiac catheterization and echo Doppler studies were performed in 22 of the 27 survivors. In 18 of 22 patients, hemodynamic data were satisfactory; a preferential direction of caval flows to both lungs was observed. Echo Doppler assessments show that forward cavopulmonary flow appears as a predominant early diastolic event, in contrast to what occurs in atriopulmonary connections. This hemodynamic model emphasizes the possible role of the diastolic ventricular performance (as a "suction pump") in Fontan circulation. Early postoperative atrial arrhythmias were observed in two of the survivors. CONCLUSIONS: The technical advantages and the hemodynamic benefits of this form of right heart bypass are encouraging. Although the use of artificial material in this procedure is extensive, none of the survivors showed thromboembolic complications or peel formations with narrowing and/or obstruction. Further investigations during a longer follow-up are needed to confirm the early and intermediate results, especially the reduction of late atrial arrhythmias.

[Endomyocardial biopsy in childhood]. / La biopsia endomiocardica in età pediatrica.

The experience with endomyocardial biopsy in pediatric age is still limited. From February 1986 to August 1990, 144 right ventricle endomyocardial biopsies were performed in 84 patients (age range 33 days--14 years, median age 31 months, weight range 3--57 kgs). Clinical diagnosis was: dilated cardiomyopathy in 50 patients; graft reject in 19; hypertrophic cardiomyopathy in 4; restrictive cardiomyopathy in 5; heart tumor in 3; ventricular arrhythmia in 3. The bioptome was introduced directly, without the use of a long sheath. There were no major complications; 2 patients experienced complete transient atrioventricular block and in 1 case right ventricular perforation occurred. In 11/45 patients (27%) with the clinical diagnosis of dilated cardiomyopathy and available myocardial specimens, acute myocarditis was diagnosed. In 47/65 procedures in the transplanted patients, a moderate to severe rejection was diagnosed. In the remaining patients, endomyocardial biopsy did not help the clinical diagnosis. We conclude that the right ventricular endomyocardial biopsy is a safe procedure in pediatric age; its utility is mostly limited to the diagnosis of acute myocarditis and graft reject after cardiac transplantation.

Cardiac catheterization through the internal jugular vein in pediatric patients. An alternative to the usual femoral vein access.

The percutaneous femoral vein approach is used routinely for cardiac catheterization in the pediatric age but in some children, it may be impossible as in the case of iliac vein or inferior vena cava thrombosis due to previous cardiac catheterization, or inconvenient as for right ventricular endomyocardial biopsies. In the period between 1982 and 1990, 160 cardiac catheterizations or right ventricular endomyocardial biopsies were performed in 102 children. Patients ranged in age between 2 months and 17 years (mean, 3.8 years) and in weight from 3.2 to 57.3 kg (mean, 14.4 kg). Indications for the internal jugular vein approach were as follows: (1) thrombosis of the inferior vena cava due to previous cardiac catheterization in 42 patients (41 percent); (2) right ventricular endomyocardial biopsy after cardiac transplant in 19 patients (19 percent); (3) control catheterization of the pulmonary arteries following classic or bidirectional cavopulmonary anastomosis in 16 patients (16 percent); (4) superior vena cava obstruction following Mustard's procedure in 14 patients (14 percent); (5) failed percutaneous femoral venous approach in six patients (6 percent); and (6) absence of the hepatic segment of the inferior vena cava in four patients (4 percent). The right or left internal jugular vein could be entered in all but three procedures (98 percent). Seventeen patients had more than one procedure through the same internal jugular vein and the vein was found patent in all. A complete right heart cardiac catheterization was performed using this route. Right ventricular endomyocardial biopsy and interventional procedure were performed through this route. Two major complications occurred. A patient developed a central transient ischemic attack and another patient developed a persistent Horner syndrome. Accidental carotid puncture occurred in five patients without consequences. Our data indicate that cardiac catheterization in infants and children can be performed safely through the internal jugular vein, with a high success rate and a low incidence of major complications.

[Anomalous insertion of the mitral valve. A rare form of subaortic obstruction in children]. / Anomala inserzione della mitrale. Una rara forma di ostruzione sottoaortica nell'infanzia.

Among different anatomical causes of subaortic obstruction, anomalous attachment of the mitral valve on ventricular septum is one of the rarest. We report our experience with 4 such cases of subaortic obstruction. Their age at first observation ranged between 1 and 6 months. All patients had viscero-atrial situs solitus, levocardia and normal atrio-ventricular and ventriculo-arterial connections. None had associated cardiac septal defects. Cases with atrio-ventricular canal were excluded. All patients showed a systolic ejection murmur and electrocardiographic features of left ventricular hypertrophy; 3 presented congestive heart failure in the first 3 months of life. Diagnosis was made by 2D-echocardiography and cardiac catheterization in 3 patients and intraoperatively in 1. Only in the last 2 patients, correct diagnosis was made at the initial 2D-echocardiographic examination. Due to left ventricular hypertrophy, in the first 2 patients hypertrophic obstructive cardiomyopathy was originally suspected. One patient died intraoperatively during attempted transaortic resection of subaortic obstruction. Other 2 patients underwent left ventricle-aortic conduit implantation. Of these 2 patients, 1 died 3 months later for sepsis and the other was reoperated upon 3 years later for mitral valve replacement and conduit take-down, with good clinical result. The fourth patient is waiting for surgical intervention. Subaortic obstruction due to anomalous attachment of the mitral valve on ventricular septum may present with early congestive heart failure; the best diagnostic tool is 2D-echocardiography. Left ventricle-aortic conduit may represent a surgical alternative to transaortic resection.