Ageing, hypertension and aortic valve stenosis - Understanding the series circuit using cardiac magnetic resonance and applanation tonometry.

BACKGROUND: Aortic stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload, but rather, functions as a series circuit, with important contributions from both the valve and vasculature. Patients with AS are typically elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizeable, and yet, quantifying this to-date has been difficult to determine. We compared measurement of aortic pressure, flow and global LV load using a cardiac magnetic resonance (CMR)/applanation tonometry (AT) technique to uncouple ventriculo-arterial (VA) interactions. METHODS: 20 healthy elderly patients and 20 with AS underwent a CMR/AT protocol. CMR provided LV volume and aortic flow simultaneously with AT pressure acquisition. Aortic pressure was derived by transformation of the AT waveform. Systemic vascular resistance (SVR) and global LV load were determined as the relationship of pressure to flow in the frequency domain. Values from both cohorts were compared. RESULTS: AS patients were older (p â€‹< â€‹0.01) albeit with no significant difference in brachial or central aortic pressure. SVR (14228 vs 19906 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) and load (740 vs 946 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) were higher in patients with AS, whilst aortic peak flow velocity was lower (38 vs 58 â€‹cm/s; p â€‹< â€‹0.01). CONCLUSIONS: Quantification of aortic pressure, flow velocity and global LV load using a simultaneous CMR/AT technique is able to demonstrate the progressive effects of hypertension and aortic stiffening with advanced age and valvular stenosis. This technique may help to better identify future patients at risk of VA coupling mismatch after correction of AS.

Peptidic biofunctionalization of laser patterned dental zirconia: A biochemical-topographical approach.

A dual approach employing peptidic biofunctionalization and laser micro-patterns on dental zirconia was explored, with the aim of providing a flexible tool to improve tissue integration of restorations. Direct laser interference patterning with a femtosecond Ti:Sapphire laser was employed, and two periodic grooved patterns were produced with a periodicity of 3 and 10 µm. A platform containing the cell-adhesive RGD and the osteogenic DWIVA peptides was used to functionalize the grooved surfaces. Topography and surface damage were characterized by confocal laser scanning (CLSM), scanning electron and scanning transmission electron microscopy techniques. The surface patterns exhibited a high homogeneity and subsurface damage was found in the form of nano-cracks and nano-pores, at the bottom of the valleys. Accelerated tests in water steam were carried out to assess hydrothermal degradation resistance, which slightly decreased after the laser treatment. Interestingly, the detrimental effects of the laser modification were reverted by a post-laser thermal treatment. The attachment of the molecule was verified trough fluorescence CLSM and X-ray photoelectron spectroscopy. Finally, the biological properties of the surfaces were studied in human mesenchymal stem cells. Cell adhesion, morphology, migration and differentiation were investigated. Cells on grooved surfaces displayed an elongated morphology and aligned along the patterns. On these surfaces, migration was greatly enhanced along the grooves, but also highly restricted in the perpendicular direction as compared to flat specimens. After biofunctionalization, cell number and cell area increased and well-developed cell cytoskeletons were observed. However, no effects on cell migration were found for the peptidic platform. Although some osteogenic potential was found in specimens grooved with a periodicity of 10 µm, the largest effects were observed from the biomolecule, which favored upregulation of several genes related to osteoblastic differentiation in all the surfaces.

Consensus guidelines for interventional cardiology services delivery during covid-19 pandemic in Australia and new Zealand.

The global coronavirus disease (COVID-19) pandemic poses an unprecedented stress on healthcare systems internationally. These Health system-wide demands call for efficient utilisation of resources at this time in a fair, consistent, ethical and efficient manner would improve our ability to treat patients. Excellent co-operation between hospital units (especially intensive care unit [ICU], emergency department [ED] and cardiology) is critical in ensuring optimal patient outcomes. The purpose of this document is to provide practical guidelines for the effective use of interventional cardiology services in Australia and New Zealand. The document will be updated regularly as new evidence and knowledge is gained with time. Goals Considerations.

Review: Comparative methane production in mammalian herbivores.

Methane (CH4) production is a ubiquitous, apparently unavoidable side effect of fermentative fibre digestion by symbiotic microbiota in mammalian herbivores. Here, a data compilation is presented of in vivo CH4 measurements in individuals of 37 mammalian herbivore species fed forage-only diets, from the literature and from hitherto unpublished measurements. In contrast to previous claims, absolute CH4 emissions scaled linearly to DM intake, and CH4 yields (per DM or gross energy intake) did not vary significantly with body mass. CH4 physiology hence cannot be construed to represent an intrinsic ruminant or herbivore body size limitation. The dataset does not support traditional dichotomies of CH4 emission intensity between ruminants and nonruminants, or between foregut and hindgut fermenters. Several rodent hindgut fermenters and nonruminant foregut fermenters emit CH4 of a magnitude as high as ruminants of similar size, intake level, digesta retention or gut capacity. By contrast, equids, macropods (kangaroos) and rabbits produce few CH4 and have low CH4 : CO2 ratios for their size, intake level, digesta retention or gut capacity, ruling out these factors as explanation for interspecific variation. These findings lead to the conclusion that still unidentified host-specific factors other than digesta retention characteristics, or the presence of rumination or a foregut, influence CH4 production. Measurements of CH4 yield per digested fibre indicate that the amount of CH4 produced during fibre digestion varies not only across but also within species, possibly pointing towards variation in microbiota functionality. Recent findings on the genetic control of microbiome composition, including methanogens, raise the question about the benefits methanogens provide for many (but apparently not to the same extent for all) species, which possibly prevented the evolution of the hosting of low-methanogenic microbiota across mammals.

Comparative analyses of tooth wear in free-ranging and captive wild equids.

REASONS FOR PERFORMING STUDY: Captive breeding has played a crucial role in the conservation of threatened equid species. Grazing ruminants and rhinoceros in captivity have less abrasion-dominated tooth wear than their free-ranging conspecifics, with potential negative consequences for their health. However, a similar study on wild equids in captivity is missing. OBJECTIVES: The aim was to establish if different tooth wear patterns are exhibited by free-ranging and captive equids. STUDY DESIGN: Cross-sectional study of museum specimens comparing free-ranging and captive equids. METHODS: Dental casts of maxillary cheek teeth of 228 museum specimens (122 from free-ranging and 106 from captive individuals) of 7 wild equid species were analysed using the extended mesowear method. Although teeth showing specific abnormalities were not scored, the presence of focal overgrowths (hooks) of the rostral premolars (106, 206) was recorded. RESULTS: Captive Equus ferus przewalskii, E. grevyi, E. hemionus, E. quagga boehmi and E. zebra hartmannae have less abrasion-dominated tooth wear on their premolars than their free-ranging conspecifics (P<0.001). Fewer differences were exhibited between populations in the molars. No differences were exhibited in the distal cusp of the molars (110, 210) between populations, except in a small sample of E. kiang. Captive equids exhibited more homogeneous wear along the tooth row whereas free-ranging equids exhibited a tooth wear gradient, with more abrasion on premolars than molars. There were more rostral hooks on the premolars (106, 206) in the captive than the free-ranging population (P = 0.02). CONCLUSIONS: Captive equids did experience less abrasion-dominated tooth wear than their free-ranging conspecifics, but the differences in tooth wear were less pronounced than those between captive and free-ranging wild ruminant and rhinoceros species. This indicates that feeding regimes for captive equids deviate less from natural diets than those for captive ruminants and rhinoceros but that factors leading to hook formation, in particular feeding height, should receive special attention. The Summary is available in Chinese - see Supporting information.

A long life among ruminants: giraffids and other special cases.

In order to investigate differences in the relative maximum longevity and other life history parameter between ruminant species, we collated data on mean body mass, maximum longevity, gestation period and newborn mass in wild ruminant and camelid species. Among ruminants, giraffids (giraffe Giraffa camelopardalis and okapi Okapia johnstoni) have particularly high longevities, long gestation periods, and low intrauterine growth rates. A particularly high absolute and relative longevity is also achieved by the anoa (Bubalus depressicornis), a member of the bovinae (cattle-type ruminants) and an insular dwarf (inhabiting the Indonesian island of Sulawesi). The fact that some (but not all) other small ruminants also achieve surprisingly high longevities leads to the hypothesis that extreme relative longevities in this group are an indication for secondary body size reduction.

Polycystic kidney disease in adult Brazilian agoutis (Dasyprocta leporina).

During the last 21 years, 7 adult captive Brazilian agoutis (Dasyprocta leporina) from 4 different zoologic gardens were necropsied and histologically examined at the Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany. All animals had polycystic kidney disease as the major pathologic change. Except in 1 case, no clinical signs were recognized prior to death. The animals had macroscopic bilateral alterations of the kidneys ranging from granulated surfaces to severe polycystic changes. Microscopic examination revealed multifocal to generalized, moderate to severe cystic dilatations of Bowman's capsules and renal tubules, moderate mesangial and capsular proliferation of the renal corpuscles, mild interstitial fibrosis, and mild to moderate interstitial lympho-plasmacytic infiltrations. Little information is known about the genetic relationships of these animals, but breeding practice indicates a high possibility of inbred agouti zoo populations in Germany. This is the first report on polycystic kidney disease in Brazilian agoutis with possible genetic background.

Integrin beta 3 expression is regulated by let-7a miRNA in malignant melanoma.

Although integrin beta(3) is known to play an important role in melanoma progression and invasion, regulation of integrin beta(3) expression in melanoma has not been analysed in detail until today. As transcriptional regulation of integrin beta(3) was ruled out by our analysis, we concentrated on the regulation by microRNAs (miRNAs). Comparing primary melanocytes and malignant melanoma cell lines, we found that one candidate miRNA, miR-let-7a, was lost in melanoma and sequence analysis suggested an interaction with the 3'-untranslated region (3'-UTR) of integrin beta(3) mRNA. Transfection of melanoma cells with let-7a pre-miR(TM) molecules resulted in the downregulation of integrin beta(3) mRNA and protein expression. In addition, we cloned the 3'-UTR of the integrin beta(3) mRNA containing the let-7a target sequence into a reporter plasmid and revealed that let-7a negatively regulates reporter gene expression. The repressed expression of integrin beta(3) accompanies with reduced invasive potential of melanoma cells transfected with synthetic let-7a molecules observed in Boyden chamber assays. On the other hand, the induction of integrin beta(3) expression was achieved in melanocytes by transfection with let-7a anti-miRs, resulting in invasive behavior of transfected melanocytes. In summary, we determined miRNA let-7a to be an important regulator of integrin beta(3) expression and showed that the loss of let-7a expression is involved in development and progression of malignant melanoma.

Long-term clinical follow-up of sirolimus-eluting (CYPHER) coronary stents in the treatment of instent restenosis in an unselected population.

Randomised trials in a highly selected patient population have demonstrated a dramatic reduction in the incidence of in-stent restenosis (ISR) following implantation of sirolimus-eluting (S-E) Cypher coronary stents compared with bare metal stents (BMS). The clinical outcome following implantation of S-E stents for treatment of complex, unselected BMS ISR is less well defined. The aim of this study was to assess the safety and efficacy of S-E coronary stents in the treatment of an unselected population of BMS ISR. All patients who received S-E stents for treatment of BMS ISR from May 1 2002-November 30 2003 at a single institution were entered into a prospectively collected database. In-hospital and long-term outcomes were collected. Sixty patients were identified who received S-E stents for the treatment of ISR. Four patients (6%) had undergone previous brachytherapy and 22% were diabetic. The most common target vessel was the left anterior descending coronary artery (40%), and 6% of lesions were in saphenous vein grafts (SVGs). The mean reference diameter was 2.67+/-0.52 (range 1.75-4.0) mm and the mean lesion length was 16.22+/-11.46 (range 3-68) mm. There were no procedural or in-hospital major adverse cardiac events (MACE). Long-term follow-up was available in 59 patients (98%). The 12-month MACE rate (cardiac death, myocardial infarction or target lesion revascularisation) was 12% with a 7% percutaneous coronary intervention rate and a 7% coronary artery bypass graft rate. There were no cardiac deaths and two non-cardiac deaths. Of the seven patients who had clinical restenosis at 12 months, four had previously failed brachytherapy and three involved SVGs. In conclusion, the use of S-E stents appears safe and efficacious in the treatment of an unselected population of BMS ISR with results comparing favourably with historical controls. Further randomised studies are needed to delineate the optimal management of this high risk group of patients.

Clinical follow-up of paclitaxel-eluting (TAXUS) stents for the treatment of saphenous vein graft disease.

BACKGROUND: Randomized trials in selected patient populations have demonstrated dramatic reductions in the incidence of in-stent restenosis (ISR) following implantation of paclitaxel-eluting (PE) coronary stents compared with bare metal stents in native coronary disease. The clinical outcome following implantation of PE stents for saphenous vein graft (SVG) stenosis is largely unknown. AIM: To assess the safety and efficacy of PE coronary stents for the treatment of SVG stenosis in an unselected population. METHODS: All patients who received PE stents for the treatment of SVG disease from May 1, 2003, to May 1, 2005, were entered into a prospectively collected database. Fifty-five patients were identified with 69 lesions. In-hospital and late major adverse cardiac events (MACE) including death, myocardial infarction (MI), and target lesion revascularization (TLR) were recorded as well as the rate of target vessel revascularization (TVR). RESULTS: Mean follow-up was 13 months with 54 of the 55 patients contacted. The number of stents implanted was 1.12 +/- 0.37 per lesion and 1.38 +/- 0.59 per patient. Clinically significant procedural MACE was 0%. The late MACE rate was 9% with a 2% clinically driven TLR, a 4% coronary artery bypass graft (CABG), and a 4% TVR rate. There were four deaths, two cardiac and two noncardiac. CONCLUSION: PE stents appear safe and effective in the treatment of SVG disease at a mean follow-up time of 13 months. Randomized studies are needed to further delineate the optimal management of this high-risk group.

Long-term follow-up of renal artery stenting in an Australian population.

BACKGROUND: Renal artery stenosis comprises both atherosclerotic renovascular disease and fibromuscular dysplasia, and may be associated with refractory hypertension, acute 'flash' pulmonary oedema and renal failure. The long-term clinical effects of renal artery stenting remain unclear. AIM: To assess the procedural and long-term safety and efficacy of renal artery stenting and its effect on blood pressure, antihypertensive medication usage and serum creatinine. METHODS: All patients referred for renal artery stenting at our institution between September 1997 and December 2003 were entered into a prospectively collected database. Systolic and diastolic blood pressure, number of antihypertensive medications, serum creatinine and estimated glomerular filtration rate (eGFR) were recorded. Patients were followed-up at least six months post-procedure. RESULTS: Eighty-nine patients underwent renal arteriography, with 110 stents deployed in 102 lesions. The procedural success rate was 99% with no procedural mortality. There were two cases of peri-procedural haemorrhage and one of sepsis. One patient developed renal and peripheral atheroemboli. FOLLOW-UP: Mean follow-up was 28 months (range 6 months-7 years). Eight patients were lost to follow-up. There were nine deaths with a mean time to death of 20.7 months (range 12 months-3 years). There was a highly statistically significant fall in systolic blood pressure (BP) from 161.7+/-29.5 mmHg pre-procedure to 138.7+/-17.9 mmHg at long-term follow-up post-procedure (p<0.0001). The clinical restenosis rate was 6.2%. Renal function and eGFR remained stable and there was a borderline significant decrease in the number of antihypertensive medications used (p=0.05). CONCLUSION: Renal artery stenting is safe and appears effective for the treatment of clinically significant renal artery stenosis.

Update on the use of stem cells for cardiac disease.

Major advances have recently been made in our understanding of stem cell biology, and in the application of stem cells to treat cardiac disease. Resident cardiac stem cells have now been described and the long-accepted paradigm of the adult mammalian heart as an organ without regenerative capacity has been questioned. Various stem-cell-based approaches for ameliorating cardiac disease have been shown to be beneficial in animal models and are now being trialled in humans, with several phase I clinical studies already completed. Although these clinical studies lacked adequate placebo controls, they have consistently shown promising results. If confirmed by larger phase II/III trials, it is possible that within a few years a powerful new therapeutic option may be available for the burgeoning number of patients suffering from myocardial ischaemia and/or other cardiac disorders.

Percutaneous carotid artery stenting: a strategy in evolution.

BACKGROUND: Carotid stenting was initially proposed as an alternative to surgical endarterectomy for selected high-risk patients. More recently, patients of standard surgical risk are being considered for percutaneous treatment of their carotid disease. AIMS: To describe the clinical outcomes of an initial consecutive cohort of patients treated by carotid stenting at one institution. METHODS: Between December 1997 and July 2003, 111 patients underwent stenting of 118 carotid arteries. Peri-procedural and long-term outcome data were collected. RESULTS: Most patients (>70%) were high-risk candidates for endarterectomy. Stents were successfully placed in 117/118 carotid arteries (99.2%). Distal protection devices were used in 43/118 (36.4%). The peri-procedural rate of death or disabling stroke was 3/118 (2.5%). Death or any stroke occurred in 11/118 (9.3%). However, only 7/118 (5.9%) procedures resulted in death or any persistent stroke (neurological deficit >1 week post-procedure). No myocardial infarction occurred. Median length of post-procedure hospitalization was 1 day. Long-term follow up was possible for 101 patients (91.0%) over a mean period of 27.1 months. The Kaplan-Meier estimate of survival free of ipsilateral stroke 36 and 66 months after carotid stenting was 77.0 +/- 9.5% and 68.2 +/- 15.1%, respectively. The estimated survival free of any stroke or stent failure was 70.9 +/- 10.7% and 60.7 +/- 17.4%, respectively. The majority of late deaths (7/11) were due to cardiac disease. CONCLUSION: We conclude that stenting of carotid stenoses is feasible, with a high procedural success rate and low complication rate. Carotid stenting should be considered the procedure of choice for high-risk patients.

Rapamycin in cardiovascular medicine.

The cellular action of rapamycin (sirolimus), a natural fermentation product produced by Streptomyces hygroscopicus, is mediated by binding to the FK506 binding protein. By inhibiting a kinase known as the target of rapamycin, it restricts the proliferation of smooth-muscle cells by blocking cell-cycle progression at the G1/S transition. The finding that rapamycin possesses both anti-proliferative and antimigratory activity suggests that it could contribute to the control of arterial re-narrowing after percutaneous intervention and control the vascular manifestations of chronic rejection in transplanted hearts. The first clinical trials of implantation of rapamycin- coated stents in obstructive coronary artery lesions have been reported and, in selected patient groups, it appears that the restenosis process has been abolished. Studies are underway to establish the benefits of rapamycin-coated stents in day-to-day interventional practice, including small vessels, long lesions and patients with multivessel disease. With the addition of novel antiplatelet agents and delivery systems, it is possible that the two major limitations of percutaneous coronary intervention - restenosis and stent thrombosis - will be overcome. Cardiac graft loss due to intimal hyperplasia and accelerated atherosclerosis remains the major limitation to long-term survival following cardiac transplantation. Animal studies of rapamycin have suggested that this process can be reduced or abolished. Human studies of the efficacy of rapamycin in preventing both acute rejection and allograft arterial disease are in progress. Concerns regarding toxicity, carcinogenicity, delayed healing and endothelialization remain. As with any new agent or technology, we must remain vigilant to late adverse side-effects.

Coronary angioplasty and Rotablator atherectomy trial (CARAT): immediate and late results of a prospective multicenter randomized trial.

Mechanical rotational atherectomy with the Rotablator is widely used for percutaneous coronary revascularization, but the ideal debulking strategy remains unknown. The purpose of this study was to compare the immediate and late results after Rotablator using two treatment strategies: Large burrs (burr/artery ratio of >0.7) to achieve maximal debulking (lesion debulking strategy) or small burrs (burr/artery ratio < or = 0.7) to modify lesion compliance (lesion modification strategy). Two hundred twenty-two patients at six centers were prospectively enrolled in this study and randomly assigned to large (n = 104 patients with 118 lesions) or small (n = 118 patients with 136 lesions) burrs. The primary endpoint was final diameter stenosis at the end of the procedure, and secondary endpoints included inhospital angiographic and clinical complications, and target lesion revascularization at 6 months. Baseline demographic and angiographic characteristics were similar. There were no differences in procedural success, the extent of immediate lumen enlargement, inhospital ischemic complications, or late target vessel revascularization. However, compared with small burrs, patients randomized to large burrs were more likely to experience serious angiographic complications (5.1% vs. 12.7%, P < 0.05) immediately after atherectomy. This study suggests that a routine lesion modification strategy employing small burrs (burr/artery ratio < or = 0.7) achieves similar immediate lumen enlargement and late target vessel revascularization compared with a more aggressive debulking strategy (burr/artery ratio >0.7), but with fewer angiographic complications.

IL-8 is an angiogenic factor in human coronary atherectomy tissue.

BACKGROUND: Interleukin-8 (IL-8), a CXC chemokine that induces the migration and proliferation of endothelial cells and smooth muscle cells, is a potent angiogenic factor that may play a role in atherosclerosis. Previously, IL-8 has been reported in atherosclerotic lesions and circulating macrophages from patients with atherosclerosis. Therefore, we sought to determine whether IL-8 plays a role in mediating angiogenic activity in atherosclerosis. METHODS AND RESULTS: Homogenates from 16 patients undergoing directional coronary atherectomy (DCA) and control samples from the internal mammary artery (IMA) of 7 patients undergoing bypass graft surgery were assessed for IL-8 content by specific ELISA, immunohistochemistry, and in situ hybridization for IL-8 mRNA. The contribution of IL-8 to net angiogenic activity was assessed using the rat cornea micropocket assay and cultured cells. IL-8 expression was significantly elevated in DCA samples compared with IMA samples (1.71+/-0.6 versus 0.05+/-0.03 ng/mg of total protein; P<0.01). Positive immunolocalization of IL-8 was found exclusively in DCA tissue sections, and it correlated with the presence of factor VIII-related antigen. In situ reverse transcriptase polymerase chain reaction revealed the expression of IL-8 mRNA in DCA tissue. Corneal neovascular response, defined by ingrowth of capillary sprouts toward the implant, was markedly positive with DCA pellets, but no constitutive vessel ingrowth was seen with IMA specimens. Neutralizing IL-8 attenuated both the in vivo corneal neovascular response and the in vitro proliferation of cultured cells. CONCLUSIONS: The results suggest that, in human coronary atherosclerosis, IL-8 is an important mediator of angiogenesis and may contribute to plaque formation via its angiogenic properties.

Validation of risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty mortality on an independent data set.

OBJECTIVES: We sought to validate recently proposed risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty (PTCA) mortality on an independent data set of high risk patients undergoing PTCA. BACKGROUND: Risk adjustment models for PTCA mortality have recently been reported, but external validation on independent data sets and on high risk patient groups is lacking. METHODS: Between July 1, 1994 and June 1, 1996, 1,476 consecutive procedures were performed on a high risk patient group characterized by a high incidence of cardiogenic shock (3.3%) and acute myocardial infarction (14.3%). Predictors of in-hospital mortality were identified using multivariate logistic regression analysis. Two external models of in-hospital mortality, one developed by the Northern New England Cardiovascular Disease Study Group (model NNE) and the other by the Cleveland Clinic (model CC), were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: In this patient group, an overall in-hospital mortality rate of 3.4% was observed. Multivariate regression analysis identified risk factors for death in the hospital that were similar to the risk factors identified by the two external models. When fitted to the data set, both external models had an area under the ROC curve >0.85, indicating overall excellent model discrimination, and both models were accurate in predicting mortality in different patient subgroups. There was a trend toward a greater ability to predict mortality for model NNE as compared with model CC, but the difference was not significant. CONCLUSIONS: Predictive models for PTCA mortality yield comparable results when applied to patient groups other than the one on which the original model was developed. The accuracy of the two models tested in adjusting for the relatively high mortality rate observed in this patient group supports their application in quality assessment or quality improvement efforts.

Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention.

OBJECTIVES: The purpose of this study was to determine the incidence of bleeding, vascular, and ischemic complications using three different heparin regimens after successful intervention. BACKGROUND: The ideal dose and duration of heparin infusion after successful coronary intervention is unknown. METHODS: Patients were randomized to one of three heparin strategies after coronary intervention: Group 1 (n = 157 patients) received prolonged (12 to 24 h) heparin infusion followed by sheath removal; Group 2 (n = 120 patients) underwent early removal of sheaths, followed by reinstitution of heparin infusion for 12 to 18 h; Group 3 (n = 137 patients) did not receive any further heparin after intervention with early sheath removal. The primary end point of the study was the combined incidence of in-hospital bleeding and vascular events. Secondary end points included in-hospital ischemic events, length of stay, cost and one-month outcome. RESULTS: After successful coronary intervention, 414 patients were randomized. Unstable angina or postinfarction angina was present in 83% of patients before intervention. The combined incidence of bleeding and vascular events was 21% in Group 1, 14% in Group 2 and 8% in Group 3 (p = 0.01). The overall incidence of in-hospital ischemic complications was 2.2%; there were no differences between groups. Length of hospital stay was shorter (p = 0.033) and adjusted hospital cost was lower (p < 0.001) for Group 3. At 30 days, the incidence of delayed cardiac and vascular events was similar for all three groups. CONCLUSIONS: Heparin infusion after successful coronary intervention is associated with more minor bleeding and vascular injury, prolonged length of stay and increased cost. In-hospital and one-month ischemic events rarely occur after successful intervention, irrespective of heparin use. Routine postprocedure heparin is not recommended, even in patients who present with unstable ischemic syndromes.

Frequency, predictors, and appropriateness of blood transfusion after percutaneous coronary interventions.

Increased awareness of the risks of blood-borne infections has recently led to profound changes in the practice of transfusion medicine. These changes include, among others, the development of guidelines by the American College of Physicians (ACP) for transfusion. Although the incidence and predictors of vascular complications of percutaneous interventions have been well defined, there are currently no data on frequency, risk factors, and appropriateness of blood transfusions. We performed a retrospective analysis of 628 consecutive percutaneous coronary revascularization procedures. Predictors of blood transfusion were identified using multivariate logistic regression analysis. Appropriateness of transfusions was determined using modified ACP guidelines. Transfusions were administered after 8.9% of interventions (56 of 628). Multivariate analysis identified age >70 years, female gender, procedure duration, coronary stenting, acute myocardial infarction, postprocedural use of heparin and intra-aortic balloon pump placement as independent predictors of blood transfusions (all p <0.05). According to the ACP guidelines, 36 of 56 patients (64%) received transfusions inappropriately. Transfusion reactions (fever) occurred in 10% of patients who received tranfusions appropriately and in 5% of patients who received tranfusions inappropriately. The estimated additional costs per procedure related to transfusions were $551 and $419, respectively. In conclusion, unnecessary transfusions were performed frequently after percutaneous coronary interventions. Application of available guidelines could reduce the number of unnecessary transfusions, thus avoiding exposure of patients to additional risks and reducing procedural costs.

The role of proto-oncogenes in coronary restenosis.

Arterial injury results in exposure of medial smooth muscle cells and adventitial fibroblasts to multiple growth factors that bind to specific cell surface receptors. These in turn activate second messengers and induce expression of immediate-early genes within minutes to hours after ligand binding to the receptor. Activation of the immediate-early genes results in passage of the stimulated cell from its nonproliferating, quiescent G0 state to the first phase of the cell cycle (G1). Coordination of the events that occur during the cell cycle is effected by a series of cyclin-dependent kinases and requires inactivation of several "tumor suppressor genes," including p53, p21, p16, p15, p27, and the retinoblastoma gene Rb, that inhibit the kinase activity of the cyclin/Cdk complexes. An understanding of the factors that regulate signal transduction, cell cycle progression, and programmed cell death has suggested several novel therapeutic strategies including (1) antisense oligonucleotide inhibition of proto-oncogene expression, (2) the use of molecular decoys or pharmacological therapies to block specific steps required for cell cycle progression, and (3) gene transfer of tumor suppressor genes. The apparent success of several of these strategies in animal models of restenosis suggests that these molecular therapies may play a valuable role in preventing intimal hyperplasia and restenosis after balloon angioplasty and vascular stenting.