Predictors of morbidity and mortality in contemporary Fontan patients: results from a multicenter study including cardiopulmonary exercise testing in 321 patients.

AIMS: previous studies have established an association between exercise intolerance and increased morbidity and mortality in congenital heart disease patients. We aimed to clarify if exercise intolerance is associated with poor outcome in Fontan patients and to identify risk factors for mortality, transplantation, and cardiac-related hospitalization. METHODS AND RESULTS: a total of 321 Fontan patients (57% male, mean age 20.9 ± 8.6 years) who underwent cardiopulmonary exercise testing (CPET) at four major European centres between 1997 and 2008 were included. During a median follow-up of 21 months, 22 patients died and 6 patients underwent cardiac transplantation (8.7%), resulting in an estimated 5-year transplant-free survival of 86%. Parameters of CPET were strongly related to increased risk of hospitalization, but-with the exception of heart rate reserve-unrelated to risk of death or transplantation. In contrast, patients with clinically relevant arrhythmia had a 6.0-fold increased risk of death or transplantation (P < 0.001). Furthermore, patients with atriopulmonary/-ventricular Fontan had a 3.7-fold increased risk of death or transplantation compared with total cavopulmonary connection patients (P= 0.009). The combination of clinically relevant arrhythmia, atriopulmonary/-ventricular Fontan, and signs of symptomatic or decompensated heart failure was associated with a particularly poor outcome (3-year mortality 25%). CONCLUSION: on short-term follow-up, most parameters of CPET are associated with increased risk of hospitalization but not death or transplantation in contemporary Fontan patients. Only decreased heart rate reserve and a history of clinically relevant arrhythmia, atriopulmonary/-ventricular Fontan, and/or heart failure requiring diuretic therapy are associated with poor prognosis, potentially identifying patients requiring medical and/or surgical attention.

[The last 50 years of pediatric cardiology (1971-2021): from Fontan operation to the present time]. / Cinquant'anni di cardiologia pediatrica (1971-2021): dall'intervento di Fontan ai nostri giorni.

Pediatric cardiology has matured profoundly over the last 50 years, paralleled by a similar development in pediatric cardiac surgery and cardiac anesthesia. This field of medicine provides structured and effective care for a very heterogeneous group of diseases including congenital heart disease, cardiomyopathies and heart failure, myocarditis, rheumatic heart disease, inherited and acquired arrhythmias, Kawasaki disease and more recently multisystemic inflammatory syndrome of children related to primary infection by SARS-CoV-2. This review summarizes achievements and results in selected topics of pediatric cardiology and cardiac surgery with focused attention to the diagnosis and management of congenital heart diseases.

Resolution of atrial thrombosis with heparin in a newborn with atrial flutter.

UNLABELLED: Atrial thrombosis is a relatively rare event in children. We report a case of a newborn with AFI who after restoration of sinus rhythm, developed atrial thrombus on a prominent Chiari network floating between the right and left atrium through the patent foramen ovale. The thrombus was resolved following treatment with heparin without events. CONCLUSION: Atrial stunning was proposed as a key mechanistic phenomenon because the thrombus occurred after the cardioversion of AFI to sinus rhythm. Heparin may be effective in the resolution of atrial thrombus within a few days.

Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients.

AIMS: We sought to assess the effects of sildenafil on exercise capacity and haemodynamic response to exercise in Fontan patients. METHODS AND RESULTS: We prospectively studied 27 patients with Fontan circulation (age 22.8 +/- 4.9 years). All patients underwent a baseline exercise test with non-invasive measurement of cardiac index (CI) and pulmonary blood flow (PBF) index, and peak exercise oxygen uptake (VO(2)). After the baseline test, patients were randomly assigned to receive either a single 0.7 mg/kg body weight oral dose of sildenafil citrate (n = 18) or no treatment (control group, n = 9). After 1 h of rest, all patients performed a second exercise test. All patients completed the study protocol. The dose of sildenafil ranged from 25 to 50 mg. The change in peak VO(2), the primary endpoint, was greater in the sildenafil group (9.4 +/- 5.2%) than in the control group (0.3 +/- 4.1%, P < 0.05). Sildenafil increased rest and peak exercise PBF index (P < 0.01 and P < 0.05 vs. control group, respectively), as well as rest and peak exercise CI (P < 0.001 and P < 0.05 vs. control group, respectively), without altering rest or peak exercise transcutaneous arterial blood oxygen saturations (P > 0.05 vs. control group for both). No patient reported serious adverse events after sildenafil. CONCLUSION: In Fontan patients, oral administration of a single dose of sildenafil improves exercise capacity and haemodynamic response to exercise.

Usefulness of cardiopulmonary exercise to predict long-term prognosis in adults with repaired tetralogy of Fallot.

Adults with tetralogy of Fallot (TOF) have increased long-term mortality. The identification of patients at greater risk for death or cardiac-related morbidity is challenging. This study was conducted to assess the prognostic value of cardiopulmonary exercise testing in adults with repaired TOF. One hundred eighteen consecutive adults with repaired TOF (mean age at repair 4.8 +/- 4.2 years) underwent cardiopulmonary exercise testing at a mean age of 24 +/- 8 years (range 16 to 59). The degree of pulmonary regurgitation, right ventricular function, and right ventricular systolic pressure were determined by transthoracic echocardiography. After the exercise tests, patients were regularly followed up for cardiac-related events. During a mean follow-up of 5.8 +/- 2.3 years (range 0.6 to 9.7), 9 patients died and 18 underwent hospitalization. Peak oxygen uptake (hazard ratio 0.974, 95% confidence interval 0.950 to 0.994), the slope of ventilation (VE) per unit of carbon dioxide production (VCO(2)) (hazard ratio 1.076, 95% confidence interval 1.038 to 1.115), and New York Heart Association functional class (hazard ratio 2.118, 95% confidence interval 1.344 to 3.542) were independent predictors of death or hospitalization. Patients with peak oxygen uptake < or =36% of predicted value and those with VE/VCO(2) slopes >39 were at greater risk for cardiac-related death (5-year mortality 48% vs 0%, p <0.0001, and 31% vs 0%, p <0.0001, respectively). In conclusion, the measurement of peak oxygen uptake and VE/VCO(2) slope in adults with repaired TOF can be prognostically important and could become a powerful tool to rationalize decisions regarding the prevention of premature sudden death and the need for reintervention.

Transcatheter patent foramen ovale closure mitigates aura migraine headaches abolishing spontaneous right-to-left shunting.

BACKGROUND: Patent foramen ovale (PFO) has been implicated in the etiology of migraine headache with aura (MHA), but the mechanisms that link right-to-left (R-to-L) shunt to MHA are unclear, and the reports on the efficacy of transcatheter PFO closure on MHA prevention are scarce. METHODS: We reviewed the clinical records of 131 consecutive patients who underwent successful transcatheter PFO closure at our institution at a mean age of 45 +/- 13 years because of cryptogenic stroke. Of the 131 patients, 35 (27%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine headache with aura incidence and severity were assessed by using Migraine Disability Assessment (MIDAS) questionnaire. Presence and magnitude of R-to-L shunt were assessed in all patients by means of transesophageal echocardiography and also by means of transcranial Doppler (TCD) in the last 50 patients (38%). RESULTS: Patients with MHA had a higher prevalence of thrombophilia (P = .007), a more complex atrial septal anatomy (P = .001), and they also had higher prevalence of spontaneous R-to-L shunt and of spontaneous large shunt, both at transesophageal echocardiography (P = .015, and .028, respectively) and at TCD (P = .036, and .038, respectively). After the procedure, 32 (91%) of 35 patients had either complete resolution or significant improvement in their MHA. At a mean follow-up of 1.7 +/- 1.3 years, MHA disappeared completely in 29 (83%) of 35 patients. Of the remaining 6 patients, 3 patients (8%) had an improvement of > or = 2 grades in the incidence and severity of MHA, 2 patients did not show any improvement of their MHA, whereas 1 patient reported a severe relapse of MHA about 1 year after the procedure. CONCLUSIONS: In patients with PFO, MHA is associated with spontaneous large R-to-L shunt and thrombophilic conditions. Transcatheter defect closure seems to be an effective and safe means to treat MHA in patients with PFO.

Relation between right ventricular structural alterations and markers of adverse clinical outcome in adults with systemic right ventricle and either congenital complete (after Senning operation) or congenitally corrected transposition of the great arteries.

This study sought to determine if areas of late gadolinium enhancement (LGE) would be present in adults with systemic right ventricles and if LGE would be associated with markers of adverse outcomes. Using gadolinium-enhanced magnetic resonance and cardiopulmonary exercise testing, 34 adults with systemic right ventricles (23 patients with atrial repair for transposition of the great arteries and 11 with congenitally corrected transposition) were studied at a mean age of 25 years. LGE was present in 14 patients (41%). The presence of LGE was associated with older age (p = 0.037), a lower right ventricular (RV) ejection fraction (34% vs 45%, p = 0.006), higher RV wall stress (p = 0.0001), reduced peak oxygen uptake (47% vs 56%, p = 0.001), and a history of arrhythmia (p = 0.005). The RV ejection fraction was correlated with RV wall stress (r = -0.81, p <0.0001) and peak oxygen uptake (r = 0.74, p <0.0001). Twelve patients experienced worsening of their clinical conditions. This was associated with decreases in biventricular function and increases in the prevalence and number of LGE areas. In conclusion, patients with systemic right ventricles have areas of abnormal myocardium, presumably due to fibrosis, that can be seen by contrast-enhanced magnetic resonance imaging. The presence of abnormal myocardial regions is associated with RV dysfunction, poor exercise tolerance, arrhythmia, and progressive clinical deterioration.

Comparison of results of percutaneous closure of patent foramen ovale for paradoxical embolism in patients with versus without thrombophilia.

We investigated the efficacy of transcatheter patent foramen ovale (PFO) closure to prevent recurrent cerebral ischemic events in patients who did and those who did not have thrombophilia. Patients who have a PFO and an associated thrombophilia may have an increased risk of cerebral ischemic events. Seventy-two consecutive patients (mean age 42 +/- 13 years) underwent percutaneous PFO closure because of a cerebral stroke (51%) or a transient ischemic attack (49%). A thrombophilia was found in 20 patients (28%). A large right-to-left shunt through the PFO was found in 44 patients (61%) and an atrial septal aneurysm was found in 39 (54%). After the first event, 18 of 20 patients (90%) with a thrombophilia received oral anticoagulation. Before closure, patients who had a thrombophilia also had a higher rate of recurrences than patients who did not (p <0.0001), despite a similar follow-up (p = 0.14) and regardless of shunt entity (p = 0.59), presence of an atrial septal aneurysm (p = 0.98), and a prevalence of cardiovascular risk factors (p = 0.44). PFO closure was successful in all patients. Five patients (8%) had a residual shunt at 6 months. At 20 +/- 11 months after PFO closure, 3 recurrent events occurred (4%), and the recurrence rate was similar in patients who did and those who did not have a thrombophilia (p = 0.25). Thus, in patients who have a cryptogenic stroke, the association of a PFO with a thrombophilia significantly increases the risk of recurrences. Thus, transcatheter PFO closure is effective for preventing recurrences in patients who have a thrombophilia.

[The ECG in pediatric patients: what the cardiologist needs to know]. / L'ECG in età pediatrica: cosa deve sapere il cardiologo dell'adulto.

During life ECG is always changing according to postnatal circulation adaptation, position of the heart in the chest, and body mass. Reference values and normal morphologies of P wave, PR interval, QRS complex, ST segment, T wave, and QTc interval are reported. Some clues to detect congenital and acquired heart diseases are also provided. Finally, a brief look at the most common diseases and arrhythmias in the neonatal and pediatric period is reported. When the pediatric ECG is too "young" for a cardiologist? When we need to stop doing the report? ... never! The baby is the father of the adult. The heart is made of signs: we have to decipher them.

Calcified Thrombus in Right Atrium: Rare but Treatable Complication of Long-term Indwelling Central Venous Catheter.

Catheter-related central thrombosis is a rare complication of long-term central line. We describe the case of an asymptomatic boy who was diagnosed a calcified thrombus in right atrium eight years after the removal of a long-term central venous device. Although the most appropriate therapeutic approach for managing floating right heart thrombi remains to be determined, surgical removal is an effective and safe procedure for calcified long-standing thrombus and it is to be preferred in elective conditions especially in young asymptomatic patients without hemodynamic involvement, that are at low risk of surgery-related morbidity and mortality.

An Unusual Case of Sinus of Valsalva Aneurysm in a GUCH Patient: An Unusual Side of the Aorto-Cardiac Fistula.

Sinus of Valsalva aneurysm can be congenital or acquired. The major complication is rupture: this can represent an evolution or an abrupt event. In case of rupture or of large aneurysm, a surgical approach is justified. We report a case of ruptured sinus of Valsalva aneurysm in a seventeen years old girl, who had underwent surgical correction of Fallot tetralogy. As soon as the rupture of sinus of Valsalva aneurysm is suspected, echocardiographic examination is the easiest and most straightforward tool to make a correct diagnosis.

[The "big heart" of carnitine]. / Il "grande cuore" della carnitina.

Fat is the primary energy source for heart muscle. In the heart, carnitine is essential for normal fatty acid beta-oxidation and even partial deficiency could lead to organ dysfunction. Dilated cardiomyopathy is one of the cardinal manifestations of carnitine deficiency in children. We report the case of a female infant referred to our hospital at the age of 15 months with a 2-week history of dyspnea. She presented signs and symptoms of congestive heart failure. Severe cardiomegaly was seen on chest radiographs, while the echocardiogram showed a dilated and hypokinetic left ventricle with depressed systolic function, decreased fractional shortening and ejection fraction, and left atrial enlargement. Laboratory investigations showed carnitine deficiency. She needed intravenous inotropic support in association with conventional heart failure therapy. Treatment with L-carnitine was started as soon as the samples for laboratory testing were taken. Cardiac function clearly and rapidly improved while on treatment.

Incompatibility between intravenous amiodarone and heparin in an infant.

Amiodarone is an effective antiarrhythmic agent and represents the drug of choice in the treatment of severe arrhythmias, especially in the setting of ventricular dysfunction. Amiodarone has the potential for interaction with many cardiac and non-cardiac drugs. Nonetheless few incompatibilities have been reported. We report the incompatibility between amiodarone and heparin administrated in the same vein in a case of a one month old baby with atrial flutter. This topic needs more attention, due to the frequent co-administration of these two drugs in tachyarrhythmias with high thromboembolic risk.

[Percutaneous aortic valvuloplasty in congenital aortic valve stenosis performed in patients older than one month: a good alternative to surgery]. / Valvuloplastica percutanea della stenosi aortica congenita oltre il primo mese di vita: una valida alternativa alla chirurgia.

BACKGROUND: Percutaneous aortic valvuloplasty is an effective means of treatment for congenital aortic valve stenosis. The aim of this study was to evaluate the immediate results of valvuloplasty, to analyze the medium to long-term outcome and to assess its efficacy in preventing or postponing a new percutaneous valvuloplasty or aortic valve surgery. METHODS: We retrospectively analyzed the reports of 37 patients aged > 1 month (mean age 6.3 years) who underwent aortic valvuloplasty for severe aortic stenosis. Associated congenital cardiac defects were present in 16% of the patients. The average time of follow-up was 5.07 years. Particular attention was focused on occurrence and progression of aortic regurgitation. RESULTS: Hemodynamic gradient after aortic valvuloplasty decreased from 58.5 to 22.5 mmHg, with an average decrease of 61.5%. On echography, the maximum gradient decreased from 93.0 to 40.5 mmHg, with an average decrease of 56.5%; mean gradient decreased from 52.0 to 20.5 mmHg with an average decrease of 60.6%. At last follow-up the average maximum and mean gradient on echo were 50.0 and 27.0 mmHg. A reintervention was needed in 21.6% of cases: a second valvuloplasty in 8.1% and aortic surgery in 13.5%. The mortality rate was 2.7%. Survival after 14 years was 97.2%; freedom from aortic valve surgery was 85.5%, from a second valvuloplasty was 89.5%, and from any type of procedure was 76.1%. CONCLUSIONS: Percutaneous aortic valvuloplasty is a safe and effective treatment for congenital aortic stenosis in patients aged > 1 month. Aortic regurgitation is the main concern in the follow-up. Nonetheless, 14 years after valvuloplasty, over 75% of patients are free from any type of aortic valve reintervention.

Determinants of exercise capacity after arterial switch operation for transposition of the great arteries.

Patients who undergo the arterial switch operation for transposition of the great arteries (TGA) are at risk of reduced exercise capacity, with most reports focusing on chronotropic incompetence as the cause. Residual right ventricular outflow tract (RVOT) obstruction is relatively common after the arterial switch operation, but its effect on exercise capacity is unknown. We studied 60 patients (44 males, age 13.3 +/- 3.4 years) who had undergone a neonatal arterial switch operation using the cardiopulmonary exercise test and transthoracic echocardiography. The peak exercise oxygen uptake (VO(2)), and heart rate were recorded and are expressed as the percentage of predicted values. The greatest velocity detected by echocardiography across the pulmonary valve, pulmonary trunk, or pulmonary branches was used in the analysis as an index of RVOT obstruction. The peak VO(2)% was 84 +/- 15%, and the peak heart rate percentage was 97 +/- 8%. Of the 60 patients, 29 had an abnormal peak VO(2)% (< or =84%) and 3 (5%) had an abnormal peak heart rate percentage (< or =85%). The maximal RVOT velocity was 2.3 +/- 0.6 m/s, and it correlated with the peak VO(2)% (r = -0.392, p = 0.004). On multivariate analysis, the presence of residual RVOT obstruction (p = 0.0007) was the only variable associated with a reduced peak VO(2)%. Patients with a RVOT maximal velocity > or =2.5 m/s had a lower peak VO(2)% than those with lower velocities (p <0.0001). No relation was found between age at testing and the peak VO(2)%. In conclusion, a reduced exercise capacity is relatively common in children and young adults who have undergone an arterial switch operation, but it does not decrease with age. The presence of residual RVOT obstruction seems to have an effect on exercise capacity.

Papillary fibroelastoma of the mitral valve in an 8-month-old infant.

Papillary fibroelastomas, the third most common primary cardiac tumor in adults, are extremely rare in children. These tumors grow slowly and are histologically benign but with high potential for life-threatening complications. We report an 8-month-old asymptomatic female infant with papillary fibroelastoma of the mitral valve, discovered by echocardiograph examination.

Impact of transverse aortic arch hypoplasia after surgical repair of aortic coarctation: an exercise echo and magnetic resonance imaging study.

BACKGROUND: We sought to assess the impact of persistent hypoplasia of the transverse aortic arch (TAA) after repair of aortic coarctation (AoC), on blood pressure response to exercise, left ventricular (LV) hypertrophy and presence of collateral circulation. METHODS: 34 consecutive patients with end-to-end repair of AoC (age at repair 3.2+/-2.5 years) underwent exercise echocardiography and magnetic resonance imaging (MRI) at 24+/-7 years of age (range 11.3 to 44.6 years). Systolic Doppler pressure gradient (SPG) across the descending aorta and blood pressure at the right arm were measured at baseline and every minute throughout all exercise. Magnetic resonance imaging was used to measure LV mass index, presence and amount of collateral flow, and the diameters of the aortic isthmus and TAA indexed to the diameter of the diaphragmatic. RESULTS: Aortic isthmus index was higher than that of the TAA (p=0.006). We observed LV hypertrophy in 15 patients (45%) and presence of collateral circulation in 14 (41%). Eighteen patients (53%) had an abnormal blood pressure response to exercise. Patients with abnormal pressure response to exercise had smaller TAA index (p=0.0005), but similar aortic isthmus index (p=0.09). They also had higher exercise SPG (p<0.0001), higher LV mass index (p<0.0001) and prevalence of LV hypertrophy (p=0.007), higher prevalence of collateral circulation (p<0.0001) and a higher amount of collateral flow (p<0.0001). TAA index, but not aortic isthmus index, correlated with exercise blood pressure (r=-0.59, p=0.003), exercise SPG (r=-0.70, p=0.0005), amount of collateral flow (r=-0.74, p=0.0002) and LV mass index (r=-0.68, p=0.0007). CONCLUSIONS: After repair of AoC, hypoplasia of the TAA may be responsible for abnormal blood pressure response to exercise, persistence of collateral circulation and LV hypertrophy.

Spontaneous large right-to-left shunt and migraine headache with aura are risk factors for recurrent stroke in patients with a patent foramen ovale.

BACKGROUND: We sought to determine whether migraine headache with aura (MHA) and spontaneous large right-to-left (R-L) shunt are risk factors for recurrent cerebral ischemic events in cryptogenic stroke patients with a patent foramen ovale (PFO). METHODS: 140 patients with a PFO and cryptogenic stroke underwent transcatheter defect closure at our institution at a mean age of 45+/-13 years. We retrospectively analyzed follow-up data from the first cerebral ischemic event to the time of PFO closure. Before the procedure, all patients underwent transesophageal echocardiography (TEE); Transcranial Doppler scanning (TCD) was additionally performed on the last 59 patients. We analyzed the impact of MHA, thrombophilia, spontaneous large R-L shunt, and atrial septal aneurysm (ASA) on the risk of recurrent cerebral ischemic events. RESULTS: 44 patients (31%) had had at least 1 recurrent event during a follow-up of 2.2+/-2.6 years. Patients with recurrent events were more commonly females (p=0.0001), had more often an associated thrombophilia (p=0.0077), and had a higher prevalence of spontaneously large R-L shunt both at TEE and at TCD (p<0.05). They also had more commonly a history of MHA (p=0.0009) and more frequent episodes of MHA (p=0.0048). Patients with MHA had a higher risk of recurrent events when compared to patients without (odds ratio 3.87, 95% CI 1.75 to 8.50). Thrombophilia (p=0.001) and spontaneous large R-L shunt (p=0.02) were independent predictors of recurrent stroke. CONCLUSIONS: In cryptogenic stroke patients with a PFO, a history of MHA, large spontaneous large R-L shunt, and thrombophilia are all associated with a higher risk of recurrent events.