Deep vein thrombosis and novel oral anticoagulants: a clinical review.

Deep vein thrombosis (DVT) is a common disease associated with high rates of mortality and significant morbidity. The diagnostic approach of DVT has evolved over the years. Algorithmical use of pretest probability, D-Dimer testing and ultrasonography allow safe and accurate investigation of DVT. The anticoagulation therapy, used to treat DVT, includes vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH) or unfractionated heparin (UF). The duration of anticoagulation therapy depends on the cause of DVT and patient's clinical profile. Although these conventional therapies are effective, narrow therapeutic index, need for frequent monitoring and various food-drug interactions cause difficulties for patients. In recent decades, new oral anticoagulants have been developed. These drugs focus directly on inhibiting either Factor Xa (rivaroxaban, apixaban, edoxaban) or thrombin (dabigatran). In contrast to warfarin, these new agents have shorter half-life, fewer drug or food interactions, no necessity for a close monitoring and ease of administration. This review summarizes current knowledge about deep vein thrombosis and new treatment aspects with novel oral anticoagulants.

Giant aneurysm of the right coronary artery with fistula to right atrium.

Coronary artery aneurysms are rare entities with a prevalence of 0.15%-4.9%. Giant coronary artery aneurysms are known as more than 2 to 5 cm in size. We present a case of 74 year-old female who was admitted to our clinic with chest pain and dyspnea. Coronary angiography demonstrated a giant right coronary artery (RCA) aneurysm with a significant left-to-right shunt. The patient underwent an open heart surgery. During the exploration, an aneurysm of 40 mm in diameter of the RCA was seen. The aneurysmatic RCA was excluded and continuously closed with the support of intra-aortic balloon pump (IABP). The patient was discharged on the 13th postoperative day without any complication.

An unusual case of retained bullet in the heart since World War II: a case report.

Although bullets penetrating into the heart are usually known as fatal, retained cardiac bullets can have a silent course without causing any cardiovascular complications. An 89 year-old patient with myocardial infarction was admitted to our department hemodynamically stable and widely awake. His electrocardiogram didn't show any evidence of ischemia. Cardiac catheterization revealed a three-vessel coronary artery disease. In addition, a circular structure projected on the area of the marginal branch and the V. magna cordis. Removal of the bullet showed that three quarters of myocardium were involved without any perforation. The history of the patient revealed an injury under the heavy fire during World War II. Thus, this case demonstrates that bullets can remain asymptomatic within in the heart for decades. The patient was dis-charged home at the 10th postoperative day after having an uneventful clinical course.

Left anterior descending coronary artery: long-term angiographic results of CABG with endarterectomy.

AIM: The procedure of coronary bypass grafting (CABG) with coronary endarterectomy (CE) is controversial. However, in the setting of severely calcified coronary arteries CE may enable complete revascularization. Complete revascularization, especially of the left anterior descending artery (LAD), is important for long-term outcome. In this study we assessed long-term LAD graft patency and anterior wall function after CABG with CE of the LAD. METHODS: Between 1984 and 1992, 283 patients underwent CABG with CE of the LAD. In 50 patients (47 men), aged 59+/-7.6 (40-77), clinical reassessment and surveillance angiography were performed. In all patients complete revascularization had been achieved with 3.5+/-1 (1-5) grafts/patient with 1-3 CE/patient. The LAD was grafted either with a saphenous vein segment (N=38) or with left intern thoracic artery (N=12). A graft obstructed less than 50% in diameter was defined as patent. RESULTS: At follow-up 39 patients (78%) were in CCS class I/II and had improved significantly (P<0.000). Control angiography after 7.6+/-2.5 (3.5-11.7) years after CABG revealed a patent LAD graft in 30/50 patients (60%). Actuarial graft patency was 100%, 96%, and 56% after 2, 5, and 10 years and was lower in patients with diabetes (P=0.001). Deterioration of anterior wall motion was observed in 17 patients (34%) and was more frequent if anterior wall motion was preoperatively normal (P=0.002), irrespective of LAD graft patency. CONCLUSION: Clinical status and long-term graft patency of grafts on endarterectomized LAD is considerable. However, patients with preoperatively normal anterior wall function are at increased risk for myocardial damage in the long-term.

Cardiac transplantation in a 14-yr-old patient with mitochondrial encephalomyopathy.

We report a rare case of a successful cardiac transplantation in a patient suffering from cardiomyopathy and complex mitochondrial disease. The patient presented with severe heart failure and malignant ventricular arrhythmias requiring implantation of a defibrillator and advanced medical treatment. The patient was listed for urgent heart transplantation and received a donor heart after 36 days. One yr post-operatively, the patient has completely recovered.

Successful single lung fontan operation in 2 children: case reports.

We report on 2 children, aged 3 and 4 years, with single ventricle physiology who underwent Fontan operation in the presence of a single right lung successfully with good midterm outcome. Therefore, the absence of one lung is not a contraindication for a Fontan palliation in selected patients with optimal hemodynamics.

Mechanical aortic and mitral valve replacement in infants and children.

BACKGROUND: The aim of this study was to evaluate early and late outcomes after mechanical systemic heart valve replacement in pediatric patients. METHODS: Between October 1981 and December 2003, 32 children (mean age 7.2 +/- 5.4 years; 4 months - 15.9 years) underwent mechanical mitral (MVR, n = 17), aortic (AVR, n = 13) or double valve replacement (DVR, n = 2) with St. Jude Medical valves. Twenty-two patients (69 %) had undergone previous cardiac surgery. Anticoagulation self-management was used since 1995. RESULTS: The operative mortality was 3.1 %. Perioperative complications were complete heart block (n = 5), ventricular fibrillation (n = 1) and myocardial infarction (n = 1) and were exclusively related to patients with MVR. Mean calculated valve size ratio (geometric prosthesis orifice area/normal valve size area) was 1.72 (1.07 - 2.85) for AVR and 1.4 (0.88 - 3.12) for MVR. Mean follow-up was 9.1 +/- 6.6 years (range 0.4 - 23.2 years, cumulative 283 patient-years). There were two late deaths in patients with MVR. Actuarial survival after 10 years was 93.8 %. Late complications were endocarditis (n = 2), minor hemorrhagic event (n = 1), and stroke (n = 1). Anticoagulation self-management is well accepted by all patients/parents. Overall 10-year freedom from any anticoagulation-related adverse event with phenprocoumon was 89.1 % (1.2 %/patient year). Nine patients required reoperations: redo-MVR (outgrowth of prostheses (n = 3), pannus overgrowth (n = 2), closure of paravalvular leak after AVR (n = 2), partial aortic valve thrombosis (n = 1) and redo-DVR (n = 1 for endocarditis). Freedom from reoperation after 10 years was 80.9 %. CONCLUSIONS: Mechanical valve prostheses are a valuable option for left-sided heart valve replacement in pediatric patients. Perioperative morbidity was exclusively related to patients with MVR. Oversizing was often possible to avoid early reoperation for outgrowth. The operative mortality and long-term morbidity are acceptable. Anticoagulation self-management is safe and well accepted.

Challenging venous reconstruction and heart transplantation in a patient with viscero-atrial situs inversus and complex congenital heart disease with Fontan circulation.

Heart transplantation represents a valuable therapeutic option for patients with congenital heart disease and end-stage heart failure. We report the case of a 15-year-old patient with situs inversus and additional complex congenital malformations of the heart who underwent several previous palliative operations. Orthotopic cardiac transplantation with several technical modifications was performed successfully. At 18 months post-operatively the patient is free from rejection and doing well in New York Heart Association (NYHA) Class I status.

Systemic mechanical heart valve replacement in children under 16 years of age.

UNLABELLED: We report the early and late outcome following left-sided mechanical heart valve replacement in children. Between 10/1981 and 02/2001, 27 children (13 male, mean age 7.2 +/- 5.2 years, range 0.53-15.7 years) underwent mechanical mitral (MVR 16), aortic (AVR 9) or double valve replacement (DVR 2) with St. Jude Medical valves. Eighteen children (66.7%) had undergone previous cardiac surgery. Valve disease was congenital in 23, due to endocarditis in 2 and rheumatic in 2 patients. Concomitant cardiac surgery was performed in 12 patients (44.4%). Operative mortality was 3.7% (1/27). Perioperative complications were complete heart block (5) and myocardial infarction (1). Mean follow-up was 6.5+/-5.9 years (range 0.4-19 years, total 169.9 patient-years). There was one valve-related late death due to mitral valve thrombosis without phenprocoumon. Actuarial survival after 1, 5 and 10 years was 93, 93 and 93%. Late complications included endocarditis (2), minor hemorrhagic event (1) and stroke (1). Overall 10-year freedom from any anticoagulation-related adverse event under phenprocoumon was 91% (1.3%/patient year). Eight patients required reoperations: re-MVR (5; outgrowth of the prostheses (3), pannus overgrowth (2)), closure of paravalvular leak after AVR (2), and re- DVR (1; endocarditis). Actuarial freedom from reoperation after 1, 5 and 10 years was 96, 88 and 76%. CONCLUSION: Mechanical valve prostheses are a valuable option for left-sided heart valve replacement in pediatric patients with good results. Operative mortality and the incidence of any valve-related events as endocarditis, reoperation, thromboembolism or anticoagulation related bleeding is acceptable.

Borderline hypoplastic left heart malformations: Norwood palliation or two-ventricle repair?

BACKGROUND: Patients with hypoplastic left heart syndrome (HLHS) and associated malformations undergo Norwood palliation or potentially a two-ventricle repair. METHODS: Since 8/99, 8 patients with typical HLHS and two with DILV underwent Norwood/Fontan palliation (group I). Three other patients (group II) had two-ventricle repair. Anatomy was: aortic atresia, coarctation, unrestrictive VSD (patient 1), hypoplastic mitral and aortic valve, arch and LV, coarctation (patients 2 and 3). Surgical procedures were Norwood arch reconstruction with either Rastelli operation (patient 1) or ASD-closure (patients 2 and 3). RESULTS: Operative mortality in group I was 1/8 (day 22; RV-failure). Two patients died before Glenn (sepsis, RV-failure). Six patients underwent Glenn procedure successfully. No patient died in group II. Echocardiography after 13 +/- 7.4 months showed mild homograft dysfunction (patient 1) and an LVOT-gradient of 20 mmHg (patient 3). Clinical condition of all survivors in both groups is good. CONCLUSION: Some anatomical subsets of HLHS with borderline mitral valves and small left ventricles may undergo two-ventricle repair despite severe LVOTO. Mortality and morbidity seem to be lower, but selection criteria are so far not defined.

Minimally invasive surgery for congenital heart defects in paediatric patients.

BACKGROUND: In selected cases, minimally-invasive approaches are favoured for the correction of congenital heart defects with regard to better cosmetic results. METHODS: Between July 1999 and April 2001, 25 children (9 male; mean age 5.8 +/- 4.1 years; mean weight 19.6 +/- 12.6 kg) were operated on using minimally invasive approaches. Diagnoses were: ASD (n = 19), VSD (n = 2), ostium primum defect (n = 3) and Tetralogy of Fallot (n = 1). Female patients with ASD underwent a limited right anterolateral thoracotomy. A ministernotomy was chosen in male patients, in patients under 6 months of age, and in patients with malformations other than ASD. Cannulation was always performed via the chest incision. RESULTS: There were no perioperative complications. Mean operation time was 3.23 +/- 0.89 h. Twelve patients were extubated immediately after surgery, mean ventilation time in the others was 12.1 +/- 11.7 h. Mean ICU stay and hospital stay were 1.5 +/- 0.75 days and 8.3 +/- 2.2 days, respectively. Follow-up (mean 4.8 +/- 4.6 months) was uneventful. CONCLUSIONS: Intracardiac repair of some congenital heart defects can be performed safely and effectively via minimally-invasive approaches. Indications are expanding towards more complex defects. Exposure for precise repair is good, additional incisions can be avoided, and cosmetic results have been excellent.

Fate of intramural coronary arteries after arterial switch operation.

BACKGROUND: To evaluate the impact of intramural coronary arteries for the peri-, postoperative and long-term course after arterial switch operation (ASO). METHODS: ASO was performed in 351 patients between 1981 and 2000 with dextrotransposition of the great arteries (d-TGA). Five patients (1.4 %) had an intramural coronary artery. Coronary transfer was performed with a collar under dissection of the commissure without longitudinal splitting of the intramural section. RESULTS: None of these patients died; the intraoperative course was uneventful, and no myocardial ischemic changes were observed. In three patients, follow-up cardiac catheterization after 5, 16 and 53 months revealed an occlusion of the intramural coronary ostium. Exercise electrocardiography and myocardial scintiscan showed myocardial ischemia. Two of these patients underwent a successful internal mammary artery bypass. CONCLUSIONS: The intramural course of coronary arteries in patients with d-TGA is rare and does not cause increased mortality or myocardial infarction rates. However, the risk of coronary occlusion over time seems to be high. Therefore, patients with this condition require selective coronary angiography and frequent exercise investigations. Revascularization with an internal mammary artery bypass may be indicated.

Systemic right ventricular failure after atrial switch operation: midterm results of conversion into an arterial switch.

BACKGROUND: Failure of the systemic right ventricle after atrial switch operation can be treated by conversion into an arterial switch operation. METHODS: Four patients, age 38 to 59 months, presented with right ventricular failure after Senning operation and ventricular septal defect closure. One patient had elevated left ventricular pressure; in the other three patients the left ventricle was retrained to a left ventricular/right ventricular pressure ratio of 0.8 or greater by pulmonary artery banding in 12 to 24 months. RESULTS: Postoperative course after arterial switch operation was prolonged, but clinical condition was good at discharge. Fractional shortening ranged from 20% to 28%. Trace-to-moderate aortic regurgitation was present; only 1 patient had preserved sinus rhythm. After a mean follow-up of 43.5 months 1 patient had died due to left ventricular dysfunction. The survivors are in New York Heart Association functional class I to II. Fractional shortening has improved (29% to 37%); aortic regurgitation has not increased. No patient has undisturbed sinus rhythm. CONCLUSIONS: Conversion of an atrial into an arterial switch is an alternative to cardiac transplantation in childhood. However, the procedure is demanding. Long-term morbidity is caused by rhythm disturbances. Aortic valve performance and left ventricular function require close observation.

Tissue engineering of heart valves: in vitro experiences.

BACKGROUND: Tissue engineering is a new approach, whereby techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional tissue in vitro and in vivo. Our laboratory has focused on the tissue engineering of heart valves, and we have fabricated a trileaflet heart valve scaffold from a biodegradable polymer, a polyhydroxyalkanoate. In this experiment we evaluated the suitability of this scaffold material as well as in vitro conditioning to create viable tissue for tissue engineering of a trileaflet heart valve. METHODS: We constructed a biodegradable and biocompatible trileaflet heart valve scaffold from a porous polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted of a cylindrical stent (1 x 15 x 20 mm inner diameter) and leaflets (0.3 mm thick), which were attached to the stent by thermal processing techniques. The porous heart valve scaffold (pore size 100 to 240 microm) was seeded with vascular cells grown and expanded from an ovine carotid artery and placed into a pulsatile flow bioreactor for 1, 4, and 8 days. Analysis of the engineered tissue included biochemical examination, enviromental scanning electron microscopy, and histology. RESULTS: It was possible to create a trileaflet heart valve scaffold from polyhydroxyalkanoate, which opened and closed synchronously in a pulsatile flow bioreactor. The cells grew into the pores and formed a confluent layer after incubation and pulsatile flow exposure. The cells were mostly viable and formed connective tissue between the inside and the outside of the porous heart valve scaffold. Additionally, we demonstrated cell proliferation (DNA assay) and the capacity to generate collagen as measured by hydroxyproline assay and movat-stained glycosaminoglycans under in vitro pulsatile flow conditions. CONCLUSIONS: Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart valve scaffold. The cells appear to be viable and extracellular matrix formation was induced after pulsatile flow exposure.

Anatomical risk factors for mortality and cardiac morbidity after arterial switch operation.

BACKGROUND: The arterial switch operation (ASO) is the treatment of choice for transposition of the great arteries. METHODS: Anatomical risk factors on mortality and morbidity were analyzed retrospectively in 312 patients who underwent ASO between 1982 and 1997. RESULTS: Survival was 95%, 92%, and 92% after 30 days, 5, and 10 years, respectively. Operative survival improved after 1990 to 97% (p < 0.001). Risk factors for operative mortality were complex anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p < 0.001). Determinants of late mortality were coronary distribution (p = 0.03), position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9 years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation, and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94% after 1, 5, and 10 years, respectively. No preoperative anatomic parameter correlated with long-term morbidity. CONCLUSIONS: ASO can be performed with low operative mortality (< 5%) and long-term morbidity. Malformations associated with complex transposition of the great arteries influence early and late mortality.

Twenty years experience with pediatric pacing: epicardial and transvenous stimulation.

OBJECTIVE: Permanent cardiac pacing in children and adolescents is rare and often occurs by means of epicardial pacing. Based on two decades of experience, operative and postoperative data of patients with epicardial and transvenous pacing were analyzed retrospectively. METHODS: Between October 1979 and December 1998, 71 patients (mean age, 5.3+/-4.2, range, 1 day-16.2 years; mean body weight, 18+/-12; range, 8-56 kg) underwent permanent pacemaker implantation. Indications were sinus node dysfunction and atrio-ventricular block following surgery for congenital heart disease (69%), or congenital atrioventricular block (31%). Pacing was purely atrial (1.4%), purely ventricular (73%), ventricular with atrial synchronization (5. 6%), or atrioventricular synchronized (20%). Epicardial pacing was established in 49 (69%), transvenous in 22 (31%) patients. Follow-up was 3.4+/-3.8 years (epicardial) and 3.0+/-4.0 years (transvenous). RESULTS: Epicardial leads were implanted in younger patients (mean age: 4.5 vs. 7.0 years, P<0.05) and preferably after surgery induced atrioventricular block (78 vs. 46%, P<0.05). The youngest patient with transvenous pacing was 1.3 years old (weight, 8.5 kg). At implantation epicardial ventricular stimulation threshold at 1.0 ms was 1.07+/-0.46 vs. 0.53+/-0.31 V (transvenous) (P<0.05). The age-adjusted rate of lead-related reoperations was significantly higher in patients with epicardial leads (P<0.05), mainly due to increasing chronic stimulation thresholds resulting in early battery depletion. In three patients who received steroid-eluting epicardial leads initial low thresholds persisted after five month to one years. In two patients with recurrent epicardial threshold increase, steroid-eluting epicardial leads led to good acute and chronic thresholds after nine to 15 month. Two post-operative death (2.8%) were probably due to a dysfunction of the (epicardial) pacing system. CONCLUSIONS: Transvenous pacing in the pediatric population is associated with a lower acute stimulation threshold and a lower rate of lead-related complications. If epicardial pacing is necessary (e. g. small body weight, special intracardiac anatomy (e.g. Fontan), impossible access to superior caval vein), steroid-eluting leads may be considered.

Results of Norwood stage I operation: comparison of hypoplastic left heart syndrome with other malformations.

OBJECTIVE: We compared the Norwood stage I operation for hypoplastic left heart syndrome and other complex malformations with ductus-dependent systemic circulation. METHODS: A retrospective study of 194 patients who underwent a Norwood stage I palliation between 1990 and 1998 was conducted. Malformations in 131 patients were classified as hypoplastic left heart syndrome, defined as aortic and mitral atresia or severe stenosis, normal segmental anatomy, intact ventricular septum, and hypoplasia of the left ventricle. Sixty three patients had other lesions: hypoplastic left ventricle with ventricular septal defect (n = 18), unbalanced complete atrioventricular canal (n = 9), complex double-outlet right ventricle (n = 14), double-inlet left ventricle (n = 11), tricuspid atresia with transposition of the great arteries (n = 6), and others (n = 5), including heterotaxia. RESULTS: Operative (>30 days) and 1-year survivals were lower for patients with hypoplastic left heart syndrome than for those with other lesions (63.4% vs 81%, P =.008, and 51.2% vs 71.4%, P =.02, respectively). The presence of a nonhypoplastic left ventricle (n = 27) was associated with higher operative and 1-year survivals (96.3% vs 64.7%, P =.002; 88.9% vs 52. 7%, P <.001). A restrictive atrial septal defect and prematurity tended to increase mortality across both groups. Cox proportional hazards regression indicated that a single right ventricle was the most important independent predictor of death (P <.001). Operative mortality for all patients undergoing the stage I procedure decreased from 38.5% (1990-1994) to 21.4% after 1994 (P =.02). CONCLUSIONS: The survival of patients with malformations other than hypoplastic left heart syndrome after the Norwood procedure is greater than for those with hypoplastic left heart syndrome. Staged palliation is valid surgical therapy in these patients, with good results in intermediate follow-up.