Identification of de novo mutations and rare variants in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart malformations, characterized by underdevelopment of the structures in the left heart-aorta complex. The majority of cases are sporadic. Although multiple genetic loci have been tentatively implicated in HLHS, no gene or pathway seems to be specifically associated with the disease. To elucidate the genetic basis of HLHS, we analyzed 53 well-characterized patients with isolated HLHS using an integrated genomic approach that combined DNA sequencing of five candidate genes (NKX2-5, NOTCH1, HAND1, FOXC2 and FOXL1) and genome-wide screening by high-resolution array comparative genomic hybridization. In 30 patients, we identified two novel de novo mutations in NOTCH1, 23 rare patients inherited gene variants in NOTCH1, FOXC2 and FOXL1, and 33 rare patients mostly inherited copy-number variants. Some of the identified variations coexisted in the same patient. The biological significance of such rare variations is unknown, but our findings strengthen the role of NOTCH pathway in cardiac valve development, indicating that HLHS is, at least in part, a 'valve' disease. This is the first report of de novo mutations associated with isolated HLHS. Moreover, the coexistence of multiple rare variants suggests in some cases a cumulative effect, as shown for other complex disease.

Shelhigh No-React porcine pulmonic valve conduit: a new alternative to the homograft.

BACKGROUND: The Shelhigh No-React pulmonic valve conduit is a new porcine conduit that is glutaraldehyde-treated and detoxified using a proprietary heparin process. In our institution it has been implanted in 25 patients. The aim of this present contribution is to evaluate the short-term follow-up after its implantation. METHODS: From November 1997 to August 1999, 25 patients (mean age, 20.2 years; range, 0.6 to 28.3 years) were operated on using this conduit. Seventeen patients underwent a Ross procedure for aortic valve disease, with the conduits implanted in anatomic position; 6 patients underwent right ventricular outflow tract reconstruction; 2 patients underwent the Rastelli operation. The follow-up was complete. Preoperative and postoperative two-dimensional echocardiography data were collected. RESULTS: There were two non-conduit-related deaths. Two conduits needed to be exchanged because of an increase in the gradient. Overall, all patients were improved in terms of New York Heart Association class. Comparison of preoperative and postoperative two-dimensional echocardiography gradient showed significant improvement. At the 30-month follow-up, no calcification was seen on the explanted conduits or on the two-dimensional echocardiography, although many of the patients are children. CONCLUSIONS: The Shelhigh conduits seem to be an alternative to homograft especially in infants. These experiences are preliminary, and longer follow-up is required.

Anterior diaphragmatic hernia misinterpreted by X-ray, echocardiography, computed tomography scanning and magnetic resonance imaging.

We report the case of a 23-year-old man who was admitted to our Division with the diagnosis of pericardial lipoma. Chest X-ray, echocardiography and magnetic resonance imaging failed to reveal an anterior diaphragmatic hernia containing a small part of the stomach with a big prehernial lipoma that were found at surgery. We believe that in all cases of suspected pericardial lipoma a diaphragmatic hernia should be expected.

[Thromboembolectomy with a Fogarty catheter. Our clinical experience]. / Tromboembolectomia con catetere di Fogarty. Nostra esperienza clinica.

BACKGROUND: The Fogarty thromboembolectomy (TE) has been considered for a long time the best treatment for acute peripheral arterial occlusion. However, recently new therapeutic options like thrombolytic agents (local or systemic) have been introduced. METHODS: A total of 66 patients who underwent Fogarty TE for acute thromboembolic limb ischemia has been retrospectively studied. Patients with documented atherosclerotic pathology who were treated with other revascularization procedures were excluded. Patients were divided into four groups: 1) upper limb embolism, 2) lower limb embolism, 3) thrombosis on atherosclerotic plaque or on a graft, 4) post-traumatic thrombosis. Twelve patients underwent Fogarty TE for upper limb thromboembolic ischemia and 54 for lower limb; 57.5% of patients had atrial fibrillation. RESULTS: Procedures were successful in 59 patients (89.4%). Further surgical procedures (bypass, arterioplasty, further embolectomy) were performed in 35.1% (19/54) of patients of groups 2 and 3 with acute lower limb ischemia. Results were very good in group 1 and 4. Seven of the 54 patients treated for lower limb ischemia underwent limb amputation (12.9%), while hospital mortality was similar for lower and upper limb (31.4 and 33.3% respectively). CONCLUSIONS: The Fogarty TE is still a good option to revascularize acute ischemic peripheral arteries with good results in a high number of patients and should be particularly used where it is possible to perform additional techniques in case of failure.

Fast-track congenital heart operations: a less invasive technique and early extubation.

BACKGROUND: Many novel techniques have been described for "minimally invasive" congenital cardiac operations to achieve an improved cosmetic result. There is little information on incorporation of such techniques into fast-track congenital heart operations. METHODS: We have developed an approach to fast-track congenital heart operations, which includes a cosmetic approach for repair of congenital heart defects without sacrificing adequate exposure or requiring specialized equipment, along with a simple approach to intraoperative anesthetic management that allows extubation in the operating room. The heart is exposed through a short midline skin incision and a full median sternotomy. The conventional technique of cannulation is performed. Between October 1997 and January 1999, 88 patients were operated on with this method. Cardiac anomalies included simple and complex ostium secundum atrial septal defect, sinus venous atrial septal defect, partial atrioventricular septal defect, simple and complex ventricular septal defect, and bicuspid aortic valve stenosis. RESULTS: There were no operative or late deaths. The majority of patients were extubated in the operating room or within 2 hours of operation. No patient underwent reoperation and the mean length of hospital stay was 3.9 days. Sternal instability or wound infection were not observed. CONCLUSIONS: We believe that our approach to fast-track congenital heart operation is safe and effective. The surgical technique provides good exposure and has excellent cosmetic results. Moreover, it is easy to learn and, if necessary, the surgeon can quickly gain direct access to the heart. The anesthetic management facilitates early tracheal extubation and a shorter duration of postoperative stay.

Revision of previous Fontan connections to total extracardiac cavopulmonary anastomosis: A multicenter experience.

BACKGROUND: Conversion to total extracardiac cavopulmonary anastomosis is an option for managing patients with dysfunction of a prior Fontan connection. METHODS: Thirty-one patients (19.9 +/- 8.8 years) underwent revision of a previous Fontan connection to total extracardiac cavopulmonary anastomosis at four institutions. Complications of the previous Fontan connection included atrial tachyarrhythmias (n = 20), progressive heart failure (n = 17), Fontan pathway obstruction (n = 10), effusions (n = 10), pulmonary venous obstruction by an enlarged right atrium (n = 6), protein-losing enteropathy (n = 3), right atrial thrombus (n = 2), subaortic stenosis (n = 1), atrioventricular valve regurgitation (n = 3), and Fontan baffle leak (n = 5). Conversion to an extracardiac cavopulmonary connection was performed with a nonvalved conduit from the inferior vena cava to the right pulmonary artery, with additional procedures as necessary. RESULTS: There have been 3 deaths. Two patients died in the perioperative period of heart failure and massive effusions. The third patient died suddenly 8 months after the operation. All surviving patients were in New York Heart Association class I (n = 20) or II (n = 7), except for 1 patient who underwent heart transplantation. Early postoperative arrhythmias occurred in 10 patients: 4 required pacemakers, and medical therapy was sufficient in 6. In 15 patients, pre-revision arrhythmias were improved. Effusions resolved in all but 1 of the patients in whom they were present before revision. The condition of 2 patients with protein-losing enteropathy improved within 30 days. CONCLUSIONS: Conversion of a failing Fontan connection to extracardiac cavopulmonary connection can be achieved with low morbidity and mortality. Optimally, revision should be undertaken early in symptomatic patients before irreversible ventricular failure ensues.

[Myocardial revascularization in dextrocardia with situs inversus]. / Rivascolarizzazione miocardica nella destrocardia con situs inversus.

BACKGROUND: The incidence of coronary artery disease in patients with dextrocardia associated with situs inversus is similar to that of the general population: Nevertheless, there are few papers regarding surgical myocardial revascularization in these patients. METHODS: We report two patients with dextrocardia and situs inversus who underwent myocardial revascularization by means of coronary artery bypass grafting, with the right internal mammary artery to the left anterior descending coronary artery in one case and with the left internal mammary artery as a free graft to the left anterior descending coronary artery associated with the repair of an aneurysm of the right coronary sinus of Valsalva in the second patient. RESULTS: There were no surgical complications; the patients were discharged on the 4th and 7th postoperative days, respectively. They are alive and well after 24 and 60 months of follow-up respectively. CONCLUSIONS: This report suggests that durable myocardial revascularization in dextrocardia with situs inversus can be successfully achieved with right or left mammary artery bypass grafting to the left anterior descending coronary artery. The advantage of using an in situ mammary artery is discussed.

[Neurologic complication of carotid thrombendarterectomy]. / Complicanze neurologiche nella tromboendoarteriectomia carotidea.

BACKGROUND AND AIMS: Carotid endarterectomy (CEA) is often carried out to prevent cerebrovascular strokes. It is obviously important that neurological morbidity of the procedure is contained within acceptable limits (< 2%). METHODS: Between January 1991 and December 1997 a total of 239 CEA were performed in 216 patients (169 males and 47 females, mean age 66.6 +/- 14.2 years; range 43-81). Angioplasty was carried out using a precoagulated Dacron patch, except in cases in which the residual diameter of the internal carotid artery was greater than 5 mm. A Javid shunt was used selectively if stump pressure < 50 mmHg. RESULTS: No major neurological complications were observed. A reversible focal neurological deficit was reported in 3 cases (1.2%). Neurological morbidity correlated to peripheral arterial occlusive disease appears to be correlated mainly with technical reasons or cerebral ischemia following clamping. CONCLUSIONS: The extensive use of angioplasty with patch and the selective use of a protective shunt improve the technical success rate of surgery, significantly helping to limit morbidity.

[Coronary disease in patients with an abdominal aortic aneurysm]. / La malattia coronarica nei pazienti affetti da aneurisma dell'aorta addominale.

The presence of coronary artery disease (CAD) evaluated with coronary angiography and eventual correction of CAD in abdominal aortic aneurysm (AAA) patients has been considered the main determinant of early and late outcome after AAA repair. This study reports our experience in CAD and AAA patients in terms of diagnosis and therapy of CAD. In a population of 126 patients (122 males, 4 females, mean age 67.5 years, range 37-81) who were candidates to elective repair for AAA with a diameter > or = 5 centimeters, we included coronary arteriography in 1) patients who were symptomatic for angina (15.9%); 2) patients with previous myocardial infarction (33.3%); 3) patients with previous coronary artery bypass (4%). We identified a group of 45 patients (35.7%) with significant CAD who had been treated before AAA surgery by coronary artery bypass grafting (CABG) in 37 cases or percutaneous coronary angioplasty (PTCA) in 8 cases. AAA repair was performed during the same hospital stay or at a later date. We did not report any morbidity and mortality related to cardiac or vascular procedures. We believe that among patients reporting cardiac symptoms (previous myocardial infarction, angina) the incidence of surgically-correctable CAD is not negligible (45/67, 67.2%). Therefore, invasive coronary study is strongly suggested in such cases to reveal and treat an eventual coronary artery stenosis prior to AAA repair. The absence of cardiac morbidity and mortality related to cardiac and vascular procedures supports this approach.

Cardiac echinococcosis causing coronary artery disease.

We report a case of cardiac echinococcosis in a patient who had sustained an acute myocardial infarction 1 month previously. The coronary angiographic study revealed an isolated complete intrinsic obstruction of the left anterior descending coronary artery in the area of the cyst. The cyst was surgically removed. Coronary artery bypass grafting was not performed because of distal myocardial scarring. Coronary arteriography should routinely be performed in all patients with cardiac echinococcosis.

Minor myocardial damage and inflammatory response after three different procedures of left anterior descending artery revascularization.

BACKGROUND: Intracoronary stenting, conventional coronary artery bypass with cardiopulmonary bypass and minimally invasive direct coronary artery bypass without extracorporeal circulation are the three accepted options for revascularizing the left anterior descending coronary artery. We compare the effects of these three procedures in terms of minor myocardial damage and systemic inflammatory response. METHODS: Ninety patients undergoing left anterior descending coronary artery revascularization with these three different techniques (thirty patients per group) were considered. Blood samples were collected preoperatively and immediately postoperatively, and then 24, 48 and 72 hours after the procedures to measure troponin I, creatine kinase, its MB fraction and C-reactive protein levels. RESULTS: Postoperative levels of troponin I and MB-creatine kinase were significantly higher in conventional coronary grafting group than in PTCA-stent and in the minimally invasive surgery groups (p < 0.0003), while in both surgery groups there were higher post-operative levels of total creatine kinase and C-reactive protein (p = 0.0001). CONCLUSIONS: Minimally invasive direct coronary artery bypass surgery and PTCA-stent are similar in terms of virtual absence of minor myocardial damage. Skeletal muscle damage and inflammatory reaction are comparable in surgical patients, but they do not appear to have any clinical relevance.

Hemoperitoneum due to spontaneous rupture of an aneurysm of the left gastroepiploic artery.

We report the case of a woman, age 65 years, who was admitted to our hospital for intense abdominal pain. Hemoglobin was 9.7 g/100 ml and computed tomography (CT) confirmed the hemorrhagic state showing intraperitoneal blood. After laparotomy a ruptured aneurysm of the left gastroepiploic artery was diagnosed. Ligation of the artery was performed with good results. This case is reported because the situs of this aneurysm is very rare.

Multiple ventricular septal defects: how and when should they be repaired?

BACKGROUND: Congenital heart lesions with multiple ventricular septal defects remain a surgical challenge. Traditional approaches often rely on either ventriculotomy for exposure or palliation with pulmonary artery banding. However, indications for repair versus palliation and for various approaches to surgical exposure are not clearly defined. METHODS: From July 1992 to January 1998, 45 patients with multiple (>/=2) ventricular septal defects (37 with associated lesions) underwent surgery. Median age was 86 days; all but 4 patients were infants. The mean number of defects was 3.7, and almost half of the patients had more than 3 defects. Apical muscular defects were present in 62% of patients. Thirty-one patients underwent primary complete repair through a right atriotomy or trans-semilunar valve approach (group 1), 8 had palliation (group 2), and 6 underwent complete repair after prior palliation elsewhere (group 3). No patient had a ventriculotomy. RESULTS: One early death occurred in a group 1 patient. Four patients who had had palliation (50%) underwent early reoperation for pulmonary artery band revision because of failure to thrive or band removal after spontaneous closure of the defects. At follow-up (median 22 months), there was 1 death in a group 2 patient (palliation) and 1 other group 2 patient required cardiac transplantation. The only late reoperation was for removal of the pulmonary artery band and closure of multiple apical defects in a group 2 (palliation) patient. No patients who underwent repair have hemodynamically significant residual defects. CONCLUSIONS: In our experience, palliation of multiple ventricular septal defects is associated with greater morbidity than primary repair. Multiple defects can almost always be repaired adequately in early infancy without ventriculotomy, although "Swiss-cheese" septum may be an indication for palliation.

Posttraumatic infrarenal abdominal aortic pseudoaneurysm.

Posttraumatic abdominal aortic pseudoaneurysm is a rare lesion. To date, fewer than 30 cases have been reported in the literature, with most of those cases involving the suprarenal aorta. Infrarenal posttraumatic abdominal aortic pseudoaneurysm following abdominal trauma has been reported in only 6 other cases. We observed such a lesion in a 62-year-old man 15 years after blunt abdominal trauma inflicted in a car accident. Back pain was the presenting symptom. Resection and Dacron graft interposition were performed without postoperative morbidity.

Intrapericardial teratoma in a newborn: a case report.

Intrapericardial teratomas are unusual tumors that often cause respiratory distress and might be lethal in the newborn. The purpose of this article is to present the clinical and pathological findings in a 12-day-old male successfully treated for a big intrapericardial teratoma. Given that the diameter of this tumor is generally related to the age at the time of diagnosis, the rarity of our case is the presence of a huge intrapericardial teratoma in a newborn. The surgical resection was lifesaving.

Levels of troponin I and cardiac enzymes after reinfusion of shed blood in coronary operations.

BACKGROUND: Reinfusion of shed blood after coronary artery bypass grafting might increase the levels of cardiac enzymes with consequent difficulties in the diagnosis of perioperative myocardial infarction. METHODS: Thirty consecutive patients undergoing coronary artery bypass grafting who bled at least 400 mL within the first 4 hours after operation underwent reinfusion of shed blood. Thirty consecutive patients who were not autotransfused served as control. All patients underwent enzyme determination (total creatine kinase, MB fraction, lactate dehydrogenase, and troponin I) in the shed blood and in circulating blood preoperatively, at arrival in the intensive care unit, and 6, 24, and 48 hours after operation. RESULTS: The shed blood contained significantly higher concentration of cardiac enzymes than the circulating blood at all time intervals (p = 0.0001). The levels of creatine kinase, its MB fraction, and lactate dehydrogenase in circulating blood were significantly elevated in patients receiving autotransfusion up to 24 hours after autotransfusion. The blood levels of troponin I were not significantly different between the two group of patients at all time points. The percent fraction of MB did not increase after autotransfusion. CONCLUSIONS: The measurement of cardiac troponin I is a useful marker for the diagnosis of perioperative myocardial infarction in patients undergoing transfusion of shed blood after coronary operation.