Drug-eluting stents and perioperative risk - more than matters of the heart?

The introduction of drug-eluting stents (DES) to interventional cardiology has been a breakthrough in the treatment of in-stent restenosis. However, the downside of reduced restenosis is a significantly prolonged and practically incalculable time to reendothelialization of thrombogenic stent-surfaces with an increased risk for coronary thrombosis. As the use of DES in non-coronary arteries (e.g. carotid, renal, infrainguinal and even cerebral arteries) is increasing, new vascular beds might be put at risk of ischemia. The practice of stopping antiplatelet drugs in a perioperative setting is highly problematic and contemporary guidelines released by scientific societies from different medical specialties have recently addressed this problem. While many case reports have reported alarming incidents of stent thrombosis, prospective clinical data are scarcely available to guide anticoagulation during the perioperative phase. This review summarizes information on the vascular biology of DES and associated adverse events based on a systematic search of the available literature in public data bases. An emphasis is put on the growing use of DES in non-coronary vessels and the associated danger of putting new vascular beds at risk of thrombotic complications.

Is the function of all cardiac valves after the arterial switch operation influenced by an associated ventricular septal defect?

A ventricular septal defect in transposition of the great arteries is frequently closely related to the cardiac valves. The valvar function after arterial switch operation of patients with transposition of the great arteries and ventricular septal defect or intact ventricular septum was compared. We analysed the function of all cardiac valves in patients who underwent the arterial switch operations pre- and post-operatively, 1 year after the procedure and on follow-up. The study included 92 patients - 64 with transposition of the great arteries/intact ventricular septum and 28 with transposition of the great arteries/ventricular septal defect. The median age at surgery was 5.5 days in transposition of the great arteries/intact ventricular septum (0-73 days) and 7.0 days in transposition of the great arteries/ventricular septal defect (4-41 days). Follow-up was 51.7 months in transposition of the great arteries/intact ventricular septum (3.3-177.3 months) and 55 months in transposition of the great arteries/ventricular septal defect (14.6-164.7 months). Neo-aortic, neo-pulmonary, and mitral valvar function did not differ. Tricuspid regurgitation was more frequent 1 year post-operatively in transposition of the great arteries/ventricular septal defect (n = 4) than in transposition of the great arteries/intact ventricular septum. The prevalence of neo-aortic regurgitation and pulmonary stenosis increased over time, especially in patients with transposition of the great arteries/intact ventricular septum. The presence of a ventricular septal defect in patients undergoing arterial switch operation for transposition of the great arteries only has a minor bearing for the development of valvar dysfunction on the longer follow-up.

Pulmonary Palacos embolism: a case report.

Instrumentation with cement-augmented pedicle screws has expanded the therapeutic spectrum. This technique is useful for the palliation of bone metastases and in generalized osteoporosis. Serious complications such as pulmonary embolism have been described following percutaneous vertebroplasty, a frequently used technique. We report the case of a 55-year-old patient with a large central Palacos embolism of the right pulmonary artery after corporectomy of the lumbar vertebrae 3 and 4 and reconstruction using autologous pelvic bone. The large Palacos embolism was removed successfully from the right pulmonary artery with extracorporeal circulation.

1-year left ventricular assist device (LVAD) experience as bridge to heart transplantation in an infant with Bland-White-Garland syndrome.

Left ventricular assist device (LVAD) implantation has become an established therapy in adults as well as in children as a bridge to heart transplantation or to aid myocardial recovery. We describe the first case worldwide of an infant suffering from Bland-White-Garland syndrome successfully treated with a left ventricular assist device (Berlin Heart(R); Excor(R) Pediatric) as a bridge to heart transplantation for a period of more than one year.

Effect of pulsatile and non-pulsatile left ventricular assist devices on the renin-angiotensin system in patients with end-stage heart failure.

INTRODUCTION: Left ventricular assist devices have been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement of their heart failure after LVAD implantation, we studied the physiological effect of pulsatile and non-pulsatile devices on the neurohormonal axis and exercise capacity. METHODS: We prospectively included 20 patients (17 men, 3 women) undergoing LVAD implantation between November 2001 and January 2004. Ten patients (1 woman and 9 men) were treated with the non-pulsatile INCOR-LVAD (Berlin Heart(c)) and ten patients received the pulsatile EXCOR LVAD (Berlin Heart(c)). Blood samples for plasma renin activity (PRA) were taken once a week over a period of ten weeks. All blood samples were collected in the morning before mobilization. Blood pressure, body weight, fluid intake and urine production were measured once a day. All patients received standard hospital diet with no limitation in fluid intake. RESULTS: Body weight remained constant in both groups throughout the ten weeks' examination, and fluid intake and urine production were balanced in all patients. Although there was no significant difference in mean blood pressure (INCOR: 70 +/- 10 mmHg; EXCOR: 73 +/- 10 mmHg), plasma renin activity was substantially elevated in patients with non-pulsatile left ventricular support (INCOR: 94.68 +/- 33.97 microU/ml; EXCOR: 17.06 +/- 15.94 microU/ml; P < 0.05). Furthermore plasma aldosterone levels were significantly higher in patients supported by non-pulsatile INCOR LVAD (INCOR: 73.4 +/- 9.6 microg/ml; EXCOR: 20.6 +/- 4.6 microg/ml; P < 0.05). CONCLUSIONS: Our data suggest that pulsatile as well as non-pulsatile left ventricular assist devices are equally able to treat chronic heart failure. However pulsatile devices seem to have a greater impact on reversing the changes in plasma renin activity and might thus offer a greater advantage when recovery of left ventricular function is expected.

Limitations of high urgency listing--ventricular assist device support in a neonate for 452 days.

The Eurotransplant International Foundation in Leiden, the Netherlands, is responsible for mediation and allocation of organ donation procedures to its member countries Austria, Belgium, Croatia, Germany, Luxembourg, the Netherlands and Slovenia. To provide organs for the patients who require urgent transplantation, the "high urgent (HU)" status was introduced in 2001 in Germany . This new HU allocation system is applicable to neonates as well as adults. However, waiting times on HU status exceed several weeks to months. Therefore an increasing number of pediatric patients has to undergo implantation of a ventricular assist device (VAD). In the present report we discuss the current Eurotransplant heart allocation system for pediatric heart transplantation in the light of a neonate with 452 days on mechanical support. We compare the average waiting time of patients on HU status at our center and their outcome in 2007 and 2008 (Data obtained from Eurotransplant International Foundation). Waiting time on HU status in our center increased significantly from 2007 to 2008. Therefore more patients require VAD support as bridging to transplantation. The case of a neonate under long-term VAD support is an outstanding example of the negative effects of this development.

Partial mechanical long-term support with the CircuLite Synergy pump as bridge-to-transplant in congestive heart failure.

BACKGROUND: Full mechanical support with a left ventricular assist device (LVAD) is often limited to very sick patients, as the only survival option. This European multicenter study analyzes the effect of partial mechanical support as bridge-to-transplant in a less sick heart failure patient group. METHODS: The CircuLite Synergy device is implanted via a small right-sided thoracotomy with an inflow cannula in the left atrium and an outflow graft connected to the right subclavian artery without the use of extracorporeal circulation. The pump itself sits in a "pacemaker" pocket subcutaneously in the right clavicular groove. It is able to pump up to 3.0 l/min and partially unload the left ventricle. RESULTS: The device was implanted in 25 patients on the cardiac transplant waiting list (20 males), aged 55.5 +/- 9.6 yrs with an ejection fraction of 21.6 +/- 6.0 %, a mean arterial pressure of 73.5 +/- 8.5 mmHg, a pulmonary capillary wedge pressure of 27.2 +/- 7.8 mmHg and cardiac index of 1.9 +/- 0.4 l/min/m (2). Duration of support ranged from 6 to 238 days. Right heart catheterization showed significant hemodynamic improvement in the short- and intermediate-term after implantation with increases in arterial pressure from 72.6 +/- 11.0 to 79.4 +/- 8.6 mmHg ( P = 0.04) and in cardiac index from 2.0 +/- 0.4 to 2.7 +/- 0.6 l/min/m (2) ( P = 0.003) with a reduction in pulmonary capillary wedge pressure from 28.5 +/- 6.0 to 19.7 +/- 6.9 mmHg ( P = 0.012). CONCLUSIONS: The CircuLite Synergy device is a partial support pump, which is easy to implant and which provides hemodynamic benefits in bridging heart failure patients to cardiac transplant.

Successful management of MRSA sepsis in a patient with left ventricular assist device.

Left ventricular assist devices (LVADs) offer the opportunity to substantially improve the clinical conditions and to interrupt hospitalization of patients suffering from end-stage heart failure awaiting heart transplantation. The authors report a case of a 66-year old patient suffering from end-stage idiopathic dilative cardiomyopathy who needed the implantation of a LVAD and later developed a sepsis with a methicillin resistant Staphylococcus aureus (MRSA) which could be recovered by a differentiated antibiotic regimen.

Fetoscopic transesophageal electrocardiography and stimulation in fetal sheep: a minimally invasive approach aimed at diagnosis and termination of therapy-refractory supraventricular tachycardias in human fetuses.

BACKGROUND: Therapy-refractory supraventricular tachycardia commonly results in hydrops and death in human fetuses. The purpose of this study in fetal sheep was to assess the feasibility of a minimally invasive fetoscopic approach for fetal transesophageal electrocardiography and stimulation aimed at diagnosis and termination of these tachycardias. METHODS AND RESULTS: We studied a total of 10 fetal sheep (87 to 103 days of gestation; term=145 days). We entered the amniotic cavity using a percutaneous fetoscopic approach and placed various electrophysiology catheters into the fetal esophagus. We recorded the number of animals in which fetoscopic transesophageal electrocardiography and stimulation were successful and assessed pacing success and thresholds for different catheters. In addition, we monitored for potential adverse effects from stimulation and for other complications of the operation. Recording of transesophageal electrocardiograms was successful in all fetal sheep. Capture during stimulation was successfully documented by additional fetal bipolar surface electrocardiograms in 7 fetuses. In fetuses in which fetal surface electrocardiograms were not recorded, pacing stimulus artifacts interfered with documentation of capture. Although stimulation thresholds were high, the maternal rhythm was not affected by fetal stimulation. CONCLUSIONS: Fetoscopic fetal transesophageal electrocardiography and stimulation are feasible in fetal sheep. This minimally invasive approach might have the potential to improve diagnosis and management of therapy-refractory supraventricular tachycardias in human fetuses.

Multimodal fetal transesophageal echocardiography for fetal cardiac intervention in sheep.

BACKGROUND: The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. METHODS AND RESULTS: We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.

Fetoscopic direct fetal cardiac access in sheep : An important experimental milestone along the route to human fetal cardiac intervention.

BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Transcription factor AP-2alpha triggers apoptosis in cardiac myocytes.

Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of unknown etiology associated with apoptosis, cardiac dilatation, progressive heart failure and increased mortality. An elevation of the transcription factor activator protein 2alpha (AP-2alpha) is involved in vertebrate embryonic development and oncogenesis. Here, we show that AP-2alpha protein is expressed in the human heart and increased in human failing myocardium with IDC. Adenovirus-mediated overexpression of human AP-2alpha triggered apoptosis and increased mRNA levels of Bcl-2 family members Bax and Bcl-x in rat cardiomyocytes. Immunohistological analysis of human myocardium revealed an increased percentage of AP-2alpha-positive nuclei in IDC and, interestingly, a colocalization of AP-2alpha-positive but not -negative cells with a caspase-cleaved fragment of poly(ADP-ribose)polymerase. We suggest AP-2alpha as a novel cardiac regulator implicated in the activation of apoptosis in IDC.

Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in stage III non-small-cell lung cancer.

PURPOSE: The objective of this prospective study was to assess the feasibility, toxicity, and efficacy of an intensive trimodality approach in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-four patients with NSCLC and biopsy-proven N2 nodes (IIIA; n = 25) or N3 nodes or T4 lesions (IIIB; n = 29) were administered two initial cycles of ifosfamide, carboplatin, and etoposide; subsequent radiotherapy (45 Gy, twice-daily 1.5 Gy) with concurrent carboplatin and vindesine; and surgery if the patient's disease was resectable or conventional radiotherapy (16 Gy, 2 Gy/d) if the patient's disease was not resectable or incompletely resectable. RESULTS: Thirty-seven patients (69%) responded to preoperative induction. Forty of 54 patients (74%) had disease that was resectable, with 34 (63%) complete resections (R0). A substantial pathologic response (tumor regression [TR] > 90%) was achieved in 27 of 54 patients (50%) and is revealed as an independent predictor for long-term survival after surgery. Five treatment-related deaths (9%) occurred. With a median follow-up period of 44 months, calculated survival rates at 3 years were 35% for patients with stage IIIA disease, 26% for patients with stage IIIB disease, and 56% for patients with R0 disease and TR > 90%. CONCLUSION: This trimodality approach is feasible and results in encouraging 3-year survival rates in prognostically unfavorable patients with stage III NSCLC. Patients experiencing a 90% degree of pathologic TR were most likely to achieve long-term survival.

The impact of anti-endotoxin core antibodies on endotoxin and cytokine release and ventilation time after cardiac surgery.

OBJECTIVES: We hypothesized that a temporary cardiopulmonary bypass (CPB)-induced reduction of endotoxin antibody levels contributes to elevated endotoxin levels and the associated inflammatory consequences, with a significant influence on the postoperative ventilation time period. BACKGROUND: Cardiac surgery using CPB induces a systemic inflammatory response syndrome with an associated risk of increased postoperative morbidity and mortality. METHODS: A total of 100 consecutive patients undergoing elective coronary artery bypass graft surgery using CPB were prospectively investigated. Endotoxin core antibodies (immunoglobulin [Ig] M/IgG against lipid A and lipopolysaccharide), endotoxin, interleukin (IL)-1-beta, IL-6, IL-8 and tumor necrosis factor-alpha were measured serially from 24 h preoperatively until 72 h postoperatively. RESULTS: Eighty-five patients had no complications (group 1), whereas 15 patients required prolonged ventilation (group 2). In both groups, there was a decrease of all antibodies 5 min after CPB onset, compared with baseline values (p < 0.001), an increase of endotoxin and IL-8 peaking at 30 min postoperatively (p < 0.001) and an increase of IL-6 peaking 3 h postoperatively (p < 0.001). In group 2, preoperative antibody levels were lower (p < 0.01)--specifically, the decrease in IgM was significantly stronger and of longer duration (p < 0.002)--and levels of endotoxin (p < 0.001) and IL-8 (p < 0.001) were higher at 30 min postoperatively. CONCLUSIONS: We conclude that an CPB-associated temporary reduction of anti-endotoxin core antibody levels contributes to elevated endotoxin and IL-8 release. Furthermore, lower levels of IgM anti-endotoxin core antibodies were associated with a greater rise in endotoxin and IL-8, as well as prolonged respirator dependence.

Harvest of the radial artery: technique of the skeletonization and pedicle preparation.

Nowadays, radial artery grafts play a significant role in coronary artery revascularization, however, harvesting techniques are not standardized. We developed various surgical techniques for radial artery harvesting considering the anatomic landmarks of the foramen, including conventional surgery (with scissors and clips) and procedures with ultrasonic scalpel and retrieving the radial artery graft in a pedicle or in a skeletonized manner.

Absence of xanthine oxidoreductase activity in human myocardium.

STUDY OBJECTIVE: The aim was to examine whether or not xanthine oxidase activity may be a significant source of oxygen derived free radicals in the human heart. DESIGN: Xanthine oxidoreductase activity of human myocardium was assayed in vitro. In addition, tests were performed to assess whether or not endogenous inhibitors of the enzyme were present in myocardial homogenates. The enzyme assay was based on high performance liquid chromatography with electrochemical and/or radiochemical detection of hypoxanthine, xanthine, and urate. SUBJECTS: Measurements were done on (a) isolated perfused rat myocardia and (b) left ventricular needle biopsies and papillary muscles obtained during elective cardiac surgery (chiefly aortic and/or mitral valve replacement and aortocoronary bypass) (n = 105 patients). MEASUREMENTS AND MAIN RESULTS: Homogenisation of human papillary muscles in buffer caused significant accumulation of hypoxanthine but not xanthine or urate. In addition, during incubation of crude myocardial homogenates with exogenous xanthine or hypoxanthine in the presence of NAD+ and/or O2 no production of urate was detected. Likewise, following aerobic incubation of papillary muscle homogenates with 14C-hypoxanthine neither 14C-xanthine nor 14C-urate were formed. Absence of xanthine oxidising activity was also observed with human papillary muscle extracts that were subjected to either ultrafiltration or gel filtration. In contrast, the rat heart was found to contain abundant xanthine oxidoreductase activity. The rat heart enzyme was inhibited by both allopurinol and oxypurinol but remained active when mixed with human papillary muscle homogenates. CONCLUSIONS: These findings show absence of xanthine oxidase and xanthine dehydrogenase activities in human myocardium, indicating that xanthine oxidase is not a source of oxygen derived free radicals in the human heart.

Comparative analysis of plasminogen activator inhibitor-1 expression in different types of atherosclerotic lesions in coronary arteries from human heart explants.

OBJECTIVES: Clinical manifestations of coronary heart disease result primarily from the progressive development of atherosclerotic plaques and subsequent thrombus formation: processes which may be accelerated by an enhanced expression of plasminogen activator inhibitor (PAI-1) in the vessel wall. In the present study, content and expression of PAI-1 were comparatively analyzed in human coronary arteries in relation to the presence and severity of atherosclerotic lesions. METHODS: Segments of coronary arteries obtained from heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. Antigen and activity levels of PAI-1 were determined in protein extracts of intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. RESULTS: Total PAI-1 antigen consistently increased from macroscopically normal areas (MNAs) to early lesions (ELs) and to maximal levels in fibrous (FPs) and calcified (CPs) plaques. No PAI activity was detected, although PAI-1 in its free form was present in all vascular specimens. Both free PAI-1 and PAI-1 complexed with plasminogen activators were significantly increased in extracts of advanced lesions. However, there was a 2-3 fold molar excess of free versus complexed PAI-1 in FPs and CPs. These findings suggest the presence of relevant amounts of PAI-1 in its substrate rather than in its inhibitor conformation in areas of advanced lesions. Compared with MNAs, PAI-1 mRNA was strongly expressed within the thickened intima of ELs. The highest PAI-1 expression was observed in FPs and CPs, being mainly localized in areas surrounding the necrotic cores in co-localization with infiltrating macrophages. CONCLUSIONS: PAI-1 content is consistently increased in relation to the severity of the lesions in atherosclerotic coronary arteries. The concomitant elevation of PAI-1 mRNA suggests that the PAI-1 increase in regulated by local synthesis in the areas of atherosclerotic lesions.

Overexpression of tissue-type plasminogen activator in atherosclerotic human coronary arteries.

UNLABELLED: The plasminogen activator (PA)/plasmin system is involved in various pathological processes that are considered important features of atherogenesis and atherothrombosis. These include the proteolysis of fibrin deposits and extracellular matrix components as well as the induction of cell migration and mitogenesis. Tissue-type PA (TPA) is a key enzyme mediating plasminogen to plasmin conversion. TPA plasma concentrations are elevated in patients with advanced atherosclerosis and correlate with an increased risk for myocardial infarction and stroke. In this study, we have analysed the content and expression of TPA in human coronary arteries and their relation to the presence and severity of atherosclerotic lesions. METHODS: Segments of coronary arteries obtained from heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. TPA was quantitatively determined in protein extracts of intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. RESULTS: PA activity entirely attributable to the presence of active TPA was consistently detected in the protein extracts. Extractable TPA antigen and activity showed a significant graded increase in relation to the presence and severity of atherosclerotic lesions. The ratios of active over total TPA were increased several-fold in extracts of advanced lesions despite a concomitant threefold increase in TPA complexed to its inhibitor PA-1. In macroscopically normal arterial segments and in early lesions, TPA was expressed in the endothelium and in colocalization with vascular smooth muscle cells (VSMCs). In advanced plaques, TPA mRNA was mainly detected in the lateral regions of the fibrous caps in association with migrating VSMCs and in the vicinity of the core areas infiltrated by CD68-positive macrophages. CONCLUSIONS: TPA content and expression is consistently increased in relation to the severity of the lesions in atherosclerotic coronary arteries. This may contribute to plaque destabilization and disruption. Conversely, the increased intramural TPA activity may counteract mural fibrin deposition.