Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial

BACKGROUND: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING: Biosensors Europe SA, Switzerland.

Functionally relevant coronary artery disease: comparison of 64-section CT angiography with myocardial perfusion SPECT

PURPOSE: To prospectively determine the accuracy of 64-section computed tomographic (CT) angiography for the depiction of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging with single photon emission computed tomography (SPECT), by using myocardial perfusion imaging as the reference standard. MATERIALS AND METHODS: All patients gave written informed consent after the study details, including radiation exposure, were explained. The study protocol was approved by the local institutional review board. In patients referred for elective conventional coronary angiography, an additional 64-section CT angiography study and a myocardial perfusion imaging study (1-day adenosine stress-rest protocol) with technetium 99m-tetrofosmin SPECT were performed before conventional angiography. Coronary artery diameter narrowing of 50% or greater at CT angiography was defined as stenosis and was compared with the myocardial perfusion imaging findings. Quantitative coronary angiography served as a reference standard for CT angiography. RESULTS: A total of 1093 coronary segments in 310 coronary arteries in 78 patients (mean age, 65 years +/- 9 [standard deviation]; 35 women) were analyzed. CT angiography revealed stenoses in 137 segments (13%) corresponding to 91 arteries (29%) in 46 patients (59%). SPECT revealed 14 reversible, 13 fixed, and six partially reversible defects in 31 patients (40%). Sensitivity, specificity, and negative and positive predictive values, respectively, of CT angiography in the detection of reversible myocardial perfusion imaging defects were 95%, 53%, 94%, and 58% on a per-patient basis and 95%, 75%, 96%, and 72% on a per-artery basis. Agreement between CT and conventional angiography was very good (96% and kappa = 0.92 for patient-based analysis, 93% and kappa = 0.84 for vessel-based analysis). CONCLUSION: Sixty-four-section CT angiography can help rule out hemodynamically relevant CAD in patients with intermediate to high pretest likelihood, although an abnormal CT angiography study is a poor predictor of ischemia.

Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements: prospective comparison with coronary angiography

AIM: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans. METHODS: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. RESULTS: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >or=50% stenosis with 89% sensitivity and 92% specificity. CONCLUSION: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

Simulation in training: one-year experience using an efficiency index to assess interventional radiology fellow training status

PURPOSE: To compare objective fellow and expert efficiency indices for an interventional radiology renal artery stenosis skill set with the use of a high-fidelity simulator. MATERIALS AND METHODS: The Mentice VIST simulator was used for three different renal artery stenosis simulations of varying difficulty, which were used to grade performance. Fellows' indices at three intervals throughout 1 year were compared to expert baseline performance. Seventy-four simulated procedures were performed, 63 of which were captured as audiovisual recordings. Three levels of fellow experience were analyzed: 1, 6, and 12 months of dedicated interventional radiology fellowship. The recordings were compiled on a computer workstation and analyzed. Distinct measurable events in the procedures were identified with task analysis, and data regarding efficiency were extracted. Total scores were calculated as the product of procedure time, fluoroscopy time, tools, and contrast agent volume. The lowest scores, which reflected efficient use of tools, radiation, and time, were considered to indicate proficiency. Subjective analysis of participants' procedural errors was not included in this analysis. RESULTS: Fellows' mean scores diminished from 1 month to 12 months (42,960 at 1 month, 18,726 at 6 months, and 9,636 at 12 months). The experts' mean score was 4,660. In addition, the range of variance in score diminished with increasing experience (from a range of 5,940-120,156 at 1 month to 2,436-85,272 at 6 months and 2,160-32,400 at 12 months). Expert scores ranged from 1,450 to 10,800. CONCLUSIONS: Objective efficiency indices for simulated procedures can demonstrate scores directly comparable to the level of clinical experience.

Preliminary results following reinforcement of the pulmonary autograft to prevent dilatation after the Ross procedure

OBJECTIVE: The Ross operation remains a controversially discussed procedure, because concern exists regarding late dilatation of the neoaortic root and progressive regurgitation of the autograft valve. We present our early experience with an external reinforcement of the autograft, which is inserted into a prosthetic Dacron graft with an artificial aortic root configuration. This detail should help to prevent neoaortic root dilatation. PATIENTS AND METHODS: Between 2006 and 2007, 12 patients (mean age 16 +/- 38 years; range 15-38 years) underwent a Ross procedure by this technique. Indications were aortic regurgitation (n = 2), aortic stenosis (n = 5), and combined aortic stenosis and insufficiency (n = 5). A bicuspid aortic valve was present in 9 patients. Balloon valvuloplasty had been performed in 7 patients. Follow-up was performed by clinical and echocardiographic examinations. RESULTS: No early or late deaths occurred in this small series, and freedom from reoperation is 100%. Echocardiographic follow-up confirmed absence of aortic insufficiency in 11 patients after a mean of 11 months (range 2-30 months). In 1 patient, a small asymmetric regurgitation jet was already observed at discharge echocardiography. As expected, no neoaortic root dilatation was observed during follow-up. All patients are in New York Heart Association class I. CONCLUSIONS: The present technique is a simple and reproducible technical step that does not require significant additional time. Inclusion of the autograft within a root prosthesis may be especially indicated in situations known for late autograft dilatation, namely, bicuspid aortic valve, predominant aortic insufficiency, and ascending aortic enlargement.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

MR findings of endocardial fibroelastosis in children

BACKGROUND: Endocardial fibroelastosis (EFE) is characterized by a diffuse white fibrous tissue lining the endocardium. The diagnosis is difficult to establish because clinical symptoms and electrocardiographic findings are nonspecific. Surgical resection of EFE requires the establishment of the diagnosis and delineation of the extent of the fibrotic changes. OBJECTIVE: To describe the use of MRI in the assessment of EFE in children. MATERIALS AND METHODS: Three children after surgery for aortic stenosis who were suspected of having EFE were evaluated by echocardiography and MRI. The MR evaluation consisted of black-blood, triple IR, bright-blood, perfusion and myocardial delayed-enhancement sequences. EFE was confirmed at surgery in all patients. RESULTS: Echocardiograms demonstrated vigorous systolic function but substantial diastolic dysfunction of the left ventricle in all. Mild endocardial brightening of the anterior septum, anterior wall, or papillary muscles was present in two. No study was thought to be diagnostic of endocardial fibrosis. On MRI EFE manifested at the endocardial surface as a rim of hypointense signal in the perfusion sequences and as a rim of hyperintense signal in the myocardial delayed-enhancement sequences. The black-blood, triple IR, and bright-blood sequences were not diagnostic. CONCLUSION: The diagnosis of EFE is difficult to establish by echocardiography. MRI using perfusion and myocardial delayed enhancement can be useful in establishing the diagnosis.

The Ross procedure in infants and young children

BACKGROUND: This study reviews our experience with the Ross procedure in infants and young children. METHODS: From September 1993 to September 2004, 52 children less than 15 years of age underwent a Ross procedure. The patients ranged in age from 4 days to 15 years old (median, 5 years). Fifteen patients (29%) were less than 2 years of age. The predominant indication for the Ross procedure was aortic stenosis. Sixteen patients underwent a Ross-Konno procedure for severe left ventricular outflow tract obstruction. Thirty-four patients had 48 previous interventions. Preoperatively, 6 patients showed severe left ventricular dysfunction, and 2 of the patients required ventilation and inotropic support. Concomitant procedures were performed in 8 patients. Three patients had a mitral valve replacement, 2 patients had a ventricular septal defect closure and an aortic arch reconstruction, 2 patients had aortic arch reconstructions, and 1 patient had resection of a coarctation and a ventricular septal defect closure. RESULTS: Patients were followed up for a median of 43 months (range, 1 to 130). Overall survival was 85% +/- 5% at 1 and 82% +/- 5% at 2, 5, and 10 years. Hospital mortality was 5 of 52 patients (9.6%). All deaths occurred in neonates or infants less than 2 months of age, who needed urgent surgery. Three patients died late of noncardiac causes. At last follow-up, all patients were classified in New York Heart Association functional class I or II. No patient had endocarditis of the autograft or the right ventricular outflow tract replacement. During the follow-up, no event of thrombembolism was observed. No patient required the insertion of a permanent pacemaker. Overall freedom from reoperation is 57% +/- 15% at 10 years. One patient required the replacement of the autograft at 6 months postoperatively. The development of mild aortic insufficiency was observed in 24 patients, and moderate aortic insufficiency in 1 patient during follow-up. Freedom from reoperation for the right ventricular outflow tract replacement is 60% +/- 15% at 10 years. CONCLUSIONS: The Ross procedure represents an attractive approach to aortic valve disease in young children. However, a high early mortality rate has to be considered when performing this procedure in neonates or infants who present in critical preoperative condition.

R2-recanalization of spontaneous carotid artery dissection

BACKGROUND AND PURPOSE: We set out to investigate the predictors and time course for recanalization of spontaneous dissection of the cervical internal carotid artery (SICAD). METHODS: We prospectively included 249 consecutive patients (mean age, 45+/-11 years) with 268 SICAD. Ultrasound examinations were performed at presentation, during the first month, and then at 3, 6, and 12 months, and clinical follow-ups after 3, 6, and 12 months. RESULTS: Of 268 SICADs, 20 (7.5%) presented with stenosis, 31 (11.6%) with 51% to 80% stenosis, 92 (34.3%) with 81% to 99% stenosis, and 125 (46.6%) with an occlusion. Antithrombotic treatment included anticoagulation in 174 (67%) patients, aspirin in 64 (24%) patients, and aspirin followed by anticoagulation or vice versa in 22 (8%) patients. Follow-up ultrasound showed normal findings in 160 (60%), stenosis in 27 (10%), 51% to 80% stenosis in 4 (1%), 81% to 99% stenosis in 26 (10%), and occlusion in 51 (19%) vessels. The rate of complete recanalization was 16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months. Initial occlusion of the dissected vessels reduced the odds of recanalization (OR, 4.0; 95% CI, 2.2-7.3; P<0.001), whereas the occurrence of local symptoms and signs only at presentation were independently associated with complete recanalization (OR, 0.4; 95% CI, 0.2-0.8; P=0.048). CONCLUSIONS: These results suggest that recanalization of SICAD occurs mainly within the first 6 months after the onset of symptoms. Initial occlusion reduces the likelihood of complete recanalization, whereas presentation with local symptoms and signs only increases it.

Esophageal strictures in adult eosinophilic esophagitis: dilation is an effective and safe alternative after failure of topical corticosteroids

Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.

Is a sustaining rod necessary for diverting loop ileostomy?

Objective: Whether or not a protective stoma reduces the rate of anastomotic leakage after distal colorectal anastomosis is still discussed controversially. It does however facilitate clinical management once leakage has occurred. Loop ileostomies seem to be associated with a lower morbidity and a better quality of life compared to loop colostomies. Generally, diverting loop ileostomies are secured at skin level by means of a supporting device in order to prevent retraction of the ileostomy into the abdomen. However, due to the supporting rod, difficulties may occur in applying a stoma bag correctly and leakage of faeces onto the skin may occur even with correct eversion of the afferent limb. Our aim was to compare morbidity and time to self-sufficient stoma-care in patients having a loop ileostomy with rod to those without rod. Methods: A total of 60 patients necessitating loop ileostomy were analyzed. Patients received surgery in of the two involved institutions according to inhouse standard procedures. 30 patients had an ileostomy with rod (VCHK Inselspital) and a further 30 without rod (KSW Winterthur). Morbidity and time to self-sufficiency regarding stoma care was analyzed during the first 90 postoperative days. Morbidity was determined according to a scoring system ranging from 0 to 4 points for any given set of possible complications (bleeding, necrosis, skin irritation, abscess, stenosis, retraction, fistula, prolapse, parastomal hernia, incomplete diversion), where 0 = no complication and 4 = severe complication. Continuous variables were expressed as median (95% Confidence Interval). For comparisons between the groups the Mann-Whitney U test was used, between categorical variables the X2 test was applied. Results: There were no significant differences in length of hospital stay or time to self-sufficient stoma-care between the groups. Although not significant, patients with a rod ileostomy had a tendency towards more stoma-related complications as well as stoma-related reoperations. The number of patients reaching total self-sufficiency regarding stoma care was higher after rodless ileostomy. Conclusion: According to our data, rodless ileostomies seemto fare just as well as those with a supporting rod, with equal morbidity rates and more patients reaching self-sufficient stoma care. Therefore routine application of a rod for diverting loop ileostomy seems unnecessary

Duplex sonographic criteria for measuring carotid stenoses

PURPOSE: The aim of this retrospective study was to determine optimal duplex sonographic criteria for use in our institution for diagnosing severe carotid stenoses and to correlate those findings with angiographic measurements obtained by the European Carotid Surgery Trial (ECST), North American Symptomatic Carotid Endarterectomy Trial (NASCET), and Common Carotid (CC) methods of grading carotid stenoses. METHODS: We analyzed the angiographic data using the ECST, NASCET, and CC methods and compared the results with the duplex sonographic findings. We then calculated the sensitivity, specificity, positive and negative predictive values, and accuracy of the duplex sonographic method. Taking these parameters into account, the optimal intrastenotic peak systolic velocity (PSV) and end diastolic velocity (EDV) were derived for diagnosing severe stenoses according to the 3 angiographic methods. RESULTS: Optimal PSV and EDV values for diagnosing a 70% or greater stenosis in our laboratory were as follows: with the NASCET method of angiographic grading of stenoses, PSV 220 cm/second or greater and EDV 80 cm/second or greater, and with the ECST and CC methods, PSV 190 cm/second or greater, and EDV 65 cm/second or greater. The optimal PSV and EDV for diagnosing a stenosis of 80% or greater with the ECST grading method were 215 cm/second or greater and 90 cm/second or greater, respectively. CONCLUSIONS: Duplex sonography is a sensitive and accurate tool for evaluating severe carotid stenoses. Optimal PSVs and EDVs vary according to the angiographic method used to grade the stenosis. They are similar for stenoses 70% or greater with the NASCET method and for stenoses 80% or greater with the ECST method.

Renal artery assessment with nonenhanced steady-state free precession versus contrast-enhanced MR angiography

PURPOSE: To prospectively assess the diagnostic accuracy of nonenhanced three-dimensional (3D) steady-state free precession (SSFP) magnetic resonance (MR) angiography for detection of renal artery stenosis (RAS), with breath-hold contrast material-enhanced MR angiography performed as the reference standard. MATERIALS AND METHODS: The study was local ethics committee approved; all patients gave written informed consent. Fifty-three patients (30 male, 23 female; mean age, 58 years) with arterial hypertension and suspected of having RAS were examined with 1.5-T 3D SSFP renal MR angiography. Stenosis grade, maximal visible vessel length, and subjective image quality were compared. Sensitivity, specificity, accuracy, and negative predictive value (NPV) were calculated on artery-by-artery and patient-by-patient bases. The significance of the results was assessed with the paired two-sided t test for continuous variables and with the marginal homogeneity test for categorical variables. Cohen kappa statistics were used to estimate interobserver agreement. RESULTS: One hundred eight renal arteries with 20 significant (>or=50%) stenoses were detected with contrast-enhanced MR angiography. At artery-by-artery analysis, sensitivity, specificity, accuracy, and NPV of nonenhanced SSFP MR angiography for RAS detection were 100%, 93%, 94%, and 100%, respectively, for observer 1 and 95%, 95%, 95%, and 99%, respectively, for observer 2. Corresponding patient-by-patient values were 100%, 92%, 94%, and 100%, respectively, for observer 1 and 100%, 95%, 96%, and 100%, respectively, for observer 2. Overestimation of stenosis grade with SSFP MR angiography resulted in six and four false-positive findings for readers 1 and 2, respectively. Mean maximal visible lengths of the renal arteries were 69.9 mm at contrast-enhanced MR angiography and 61.1 mm at SSFP MR angiography (P<.001). Both techniques yielded good to excellent image quality. CONCLUSION: Slab-selective inversion-prepared 3D SSFP MR angiography had high sensitivity, specificity, accuracy, and NPV for RAS detection, without the need for contrast material. However, RAS severity was overestimated in some patients.

[Treatment of the aortic valve and ascending aorta. The significance of reconstructive methods on the aortic root]

BACKGROUND AND OBJECTIVE: The standard surgical repair of disease of the aortic valve and the ascending aorta has been combined replacement, which includes the disadvantage of inserting a mechanical valve. We have investigated an individualized approach which preserves the native valve. PATIENTS AND METHODS: Between October 1995 and October 1997, a consecutive total of 101 patients (72 men, 29 women, aged 21-83 years) underwent operations for disease of the ascending aorta: aortic dissection type A in 34 patients, aneurysmal dilatation in 67. Dilatation of the aortic arch was associated with aortic regurgitation in 58 patients. There were 11 patients with aortic valve stenosis or previously implanted aortic valve prosthesis among a total of 46 whose aortic valve was replaced (group II). Supracommissural aortic replacement with a Dacron tube was performed in 16 patients (group I) with normal valve cusps and an aortic root diameter < 3.5 cm. In 28 patients with an aortic root diameter of 3.5-5.0 cm the aortic root was remodelled (group III). Resuspension of the native aortic valve was undertaken in 11 patients with aortic root dilatation of > 5.0 cm (group IV). RESULTS: Operative intervention was electively performed in 72 patients, without any death. Of 29 patients operated as an emergency for acute type A dissection four died (14%). In 55 of the 58 patients with aortic regurgitation in proved possible to preserve native aortic valve (95%). In the early postoperative phase and after an average follow-up time of 11.8 months, transthoracic echocardiography demonstrated good aortic valve function, except in one patient each of groups III and IV who developed aortic regurgitation grades I or II. CONCLUSION: The described individualized approach makes it possible to preserve the native aortic valve in most patients with aortic regurgitation, at a low risk. Follow-up observations so far indicate good results of the reconstruction.

Preoperative corticosteroids. A contraindication to lung transplantation?

Regular preoperative application of corticosteroids has been considered as a contraindication to lung transplantation for fear of an increased risk of postoperative morbidity and mortality. Recently, however, we have accepted patients for transplantation in whom treatment with steroid medication could not be terminated preoperatively. Up to February 1991, 27 unilateral and bilateral transplantations in 26 patients were analyzed. Corticosteroid therapy was discontinued at least three months prior to transplantation in 13 patients (group 1), whereas in 14 cases, the patients continued their daily corticosteroid therapy to the time of transplantation (prednisolone, 0.1 to 0.3 mg/kg/day; group 2). There were no significant differences between the groups with respect to sex, age, diagnosis, or type of transplantation. One limited bronchial dehiscence occurred; the incidence of postoperative bronchial stenosis was identical in both cohorts; one patient died in each group. In conclusion, no increased morbidity or mortality could be found following lung transplantation with regular preoperative administration of prednisolone up to 0.3 mg/kg/day. Thus, patients who cannot be weaned from their steroid medication but who otherwise are acceptable candidates should not be excluded from lung transplantation.