Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. METHODS: Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T(0)), immediately after (T(1)), 30 minutes (T(2)), 60 minutes (T(3)) and 120 minutes (T(4)) after primary PCI. RESULTS: The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T(1) (p=0.006) and T(4) (p<0.0001). CONCLUSION: The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.).

Long-term follow-up of coronary angioplasty in patients with diabetes compared with nondiabetics.

BACKGROUND: Some reports have indicated that in patients with diabetes mellitus and multivessel disease, coronary artery bypass surgery is preferred over percutaneous coronary intervention (PCI). We retrospectively compared outcome PCI in diabetic and nondiabetic patients. METHODS: Ninety-seven diabetics and 971 nondiabetics were included and randomised before PCI to aspirin alone or aspirin plus coumadin. Fifty diabetics and 481 nondiabetics underwent follow-up angiography. The primary endpoint comprised all-cause mortality, myocardial infarction or targetvessel revascularisation. RESULTS: Baseline characteristics were similar between the groups except for significantly more males and smokers among the nondiabetics. The diabetics had significantly more previous strokes, more left anterior descending coronary artery disease as well as more restenotic lesions and multivessel disease. At 30 days, the primary endpoint had occurred in five diabetics (5.2%) and 47 nondiabetics (4.9%), (p=0.8) and at one year in 17 (17.5%) and in 165 (17.1%), respectively (p=0.9). Event-free survival remained comparable during long-term follow-up (four years). Multivariate analysis showed no differences for the occurrence of any event (p=0.9, 95% CI 0.6-1.7). At six months, the minimal luminal diameter was significantly smaller in the diabetics (1.55±0.76 mm vs. 1.78±0.66 mm, p=0.01). Diabetics also had more restenosis (41% vs. 23%, p=0.003). CONCLUSION: Despite angiographical differences at six months between the diabetics and nondiabetics, both short-term and long-term clinical follow-up appeared to be similar.

The predictive value of chronic atrial fibrillation for the short- and long-term outcome after percutaneous mitral balloon valvotomy.

BACKGROUND AND AIM OF THE STUDY: The predictive value of chronic atrial fibrillation (AF) before percutaneous mitral balloon valvotomy (PMBV) is still under discussion. The effect of the duration of chronic AF on short- or long-term results is not known. Therefore, we analyzed the predictive value of pre-procedural chronic AF and the duration of this rhythm disturbance for short- and long-term outcome after PMBV in patients with mitral valve stenosis. METHODS: A total of 140 PMBV procedures was performed in 137 patients with severe mitral stenosis. Sixty-three patients (45%) were in chronic AF; in 40 patients (63%) the AF was of more than one year duration. A successful procedure is defined as PMBV achieved without acute mitral valve replacement, and a mitral valve area after PMBV of > or =1.5 cm2. RESULTS: Patients in chronic AF were significantly older, had a larger left atrial diameter and higher NYHA functional class, compared with patients in sinus rhythm (SR). The success rates of PMBV were 80.5% and 77.6% in patients with SR and AF, respectively (p = NS). Mean follow up was 4.2+/-2.6 years (n = 127). At four years' follow up the event-free survival was 86.5% in patients with SR, and 78.5% in those with chronic AF at baseline (p = 0.031). Multivariate analysis of the entire study population showed the presence of chronic AF to be the only pre-procedural independent predictor for severe mitral regurgitation after PMBV (p = 0.030), as well for an event (p = 0.039) and restenosis (p = 0.034) during follow up. The risk for an event or restenosis during follow up increased seven-fold when chronic AF at baseline was present for more than one year (p = 0.010). CONCLUSION: Pre-procedural chronic AF is an independent predictor for unfavorable outcome at short- and long-term follow up after PMBV. A longer duration of AF further increases the risk of an event or restenosis.

Combined off-pump coronary surgery and right lung resections through midline sternotomy.

Concomitant severe coronary artery disease and lung malignancies are uncommon. Combining conventional coronary surgery with cardiopulmonary bypass with lung resection is still a controversial issue. Conversely, combining off-pump coronary surgery with right lung resections through a midline sternotomy can be an attractive approach. Off-pump coronary surgery avoids the risks of cardiopulmonary bypass, reduces systemic inflammatory response and does not affect the immune system. We report a series of three patients successfully operated using this approach.

Effect of coumarins started before coronary angioplasty on acute complications and long-term follow-up: a randomized trial.

BACKGROUND: Coronary angioplasty frequently creates a thrombogenic surface, with subsequent mural thrombosis that may lead to acute complications and possibly stimulates the development of restenosis. Whether coumarins can prevent these complications is unclear. The objective of this open, randomized trial was to assess the clinical effect of coumarins started before coronary angioplasty and continued for 6 months. METHODS AND RESULTS: Before coronary angioplasty, 530 patients were randomly assigned to aspirin plus coumarins and 528 patients to aspirin alone. At the start of the angioplasty, the mean international normalized ratio was 2.7+/-1.1; during follow-up, it was 3.0+/-1.1. At 30 days, the composite end point of death, myocardial infarction, target-lesion revascularization, and stroke was observed in 18 patients (3.4%) treated with aspirin plus coumarin compared with 34 patients (6.4%) treated with aspirin alone (relative risk, 0.53; 95% CI, 0.30 to 0.92). At 1 year, these figures were 14.3% and 20.3%, respectively (relative risk, 0.71; 95% CI, 0.54 to 0.93). The incidence of major bleeding and false aneurysm during hospitalization was 3.2% and 1.0%, respectively (relative risk, 3.39; 95% CI, 1.26 to 9.11). The benefit of coumarins was observed in both stented and nonstented patients. CONCLUSIONS: Coumarins in addition to aspirin started before PTCA and continued for 6 months was more effective than aspirin alone in the prevention of acute and late complications after coronary angioplasty. This benefit was accompanied by a small but significant increase in bleeding complications.

Aortic root replacement with the pulmonary autograft: an invariably competent aortic valve?

BACKGROUND: Pulmonary autograft aortic root replacement was used in adults. Risk factors for aortic regurgitation (AR), and for pulmonary allograft valve stenosis are identified. METHODS: From February 1991 through April 1998, 80 adults (mean age 34.4 years) underwent pulmonary autograft aortic root replacement. Primary diagnosis was AR in 43 (53.7%) patients, aortic stenosis in 13 (16.3%) and mixed disease in 24 (30%) patients. A root reinforcement ring was used in 32 (40%) patients. RESULTS: There was no hospital mortality. Estimated patient survival is 100% at 7 years. A total of 3 patients underwent reoperation: 2 on the autograft for severe AR, 1 for pulmonary allograft stenosis. Freedom from reoperation on the autograft is 96.7 +/- 2.4% at 7 years. Multivariate analysis indicated bicuspid aortic valve disease as an incremental risk factor for AR at discharge (p = 0.036, odds 3.5). Univariate analysis identified operation for pure AR as risk factor for AR during follow-up (p = 0.041). Mild AR or more increased from 2.5% at discharge to 11.3% during follow-up (p = 0.008). Progression of AR was limited by the use of a reinforcement root ring (p = 0.031). Freedom from mild AR or more in patients with and without a reinforcement root ring was 100% and 72.9 +/- 9.3% respectively, at 5 years (p = 0.119). Pulmonary allograft stenosis occurred in 15 (22.5%) patients. Multivariate analysis revealed that large sized pulmonary allografts were less prone to stenosis (p = 0.048, odds 0.13). CONCLUSIONS: Pulmonary autograft root replacement can be performed with few complications. During follow-up, a significant increase in mild AR or more is observed. The use of a reinforcement root ring is effective in preventing progression of AR.

Cryopreserved aortic allografts for aortic root reconstruction: a single institution's experience.

BACKGROUND: An evaluation of early and long-term results of aortic root replacement with cryopreserved aortic allografts and echocardiographic follow-up of allograft valve function was performed. METHODS: From September 1989 through May 1998, 132 patients aged 17 to 77 years (mean, 50.8 +/- 14.8 years) underwent freestanding aortic root replacement with a cryopreserved aortic allograft. Eighty-six (65.1%) patients had New York Heart Association class III or IV functional status before operation, and 27 (20.5%) patients underwent emergency operation. Fifty-nine (44.7%) patients had undergone previous cardiac operations. The cause of aortic disease was acute endocarditis in 63 (47.7%) patients, healed endocarditis in 15 (11.3%), degenerative in 20 (15.2%), congenital in 20 (15.2%), failed prosthesis in 10 (7.6%) and rheumatic in 4 (3.0%). Follow-up was complete, with a mean of 42 months. RESULTS: There were 12 hospital deaths (9.1%; 70% confidence limits [CL], 6.6% and 11.6%); 9 of them were operated on for active endocarditis (p = 0.062). Multivariate analysis determined age older than 65 years (p = 0.012) and emergency operation (p = 0.009) as independent risk factors for hospital mortality. During follow-up, 6 (5.0%; 70% CL, 3.0% and 7.0%) patients died. Cumulative survival rate for the entire group was 81.8% +/- 5.4% at 8 years. Freedom from reoperation for structural valve failure was 100%, freedom from reoperation for any cause was 96.3% +/- 1.8% at 8 years. Freedom from endocarditis at 8 years was 97.9% +/- 1.4%. Follow-up of allograft valve function showed no or trivial aortic regurgitation in 97% of patients and absence of stenosis of the allograft in 100%. CONCLUSIONS: Aortic root replacement with cryopreserved aortic allografts can be performed with acceptable hospital mortality and long-term results. The durability of cryopreserved aortic allografts is good, and reoperation for structural valve failure is absent at 8 years.

Laser angioplasty of restenosed coronary stents: results of a multicenter surveillance trial. The Laser Angioplasty of Restenosed Stents (LARS) Investigators.

OBJECTIVES: This study evaluated safety and efficacy of excimer laser angioplasty for treatment of restenosed or occluded coronary stents. BACKGROUND: Balloon angioplasty of in-stent restenosis is limited by a high recurrence rate. Debulking by laser angioplasty is a novel concept to treat in-stent restenosis. METHODS: A total of 440 patients with restenoses or occlusions in 527 stents were enrolled for treatment with concentric or eccentric laser catheters and adjunctive balloon angioplasty. RESULTS: Laser angioplasty success (< or =50% diameter stenosis after laser treatment or successful passage with a 2.0-mm or 1.7-mm eccentric laser catheter) was achieved in 92% of patients. Adjunctive balloon angioplasty was performed in 99%. Procedural success (laser angioplasty success followed by < or =30% stenosis with or without balloon angioplasty) was 91%. There was neither a significant difference in success with respect to lesion length, nor were there differences between small and large vessels or native vessels and vein grafts. Success was higher and residual stenosis lower using large or eccentric catheters. Serious adverse events included death (1.6%, not directly laser catheter related), Q-wave myocardial infarction (0.5%), non-Q-wave infarction (2.7%), cardiac tamponade (0.5%) and stent damage (0.5%). Perforations after laser treatment occurred in 0.9% of patients and after balloon angioplasty in 0.2%. Dissections were visible in 4.8% of patients after laser treatment and in 9.3% after balloon angioplasty. Reinterventions during hospitalization were necessary in 0.9% of patients; bypass surgery was performed in 0.2%. CONCLUSIONS: Excimer laser angioplasty with adjunctive balloon angioplasty is a safe and efficient technology to treat in-stent restenoses. These data justify a randomized comparison with balloon angioplasty.

Predictors of clinical events or restenosis during follow-up after percutaneous mitral balloon valvotomy.

AIMS: The purpose of this study is to define predictors of events or restenosis during follow-up after percutaneous mitral balloon valvotomy. METHODS AND RESULTS: Percutaneous mitral balloon valvotomy was attempted in 137 patients with severe mitral valve stenosis. In 127 patients follow-up was complete with a mean of 4.2 +/- 2.6 years. Events during follow-up were defined as death, mitral valve surgery or repeat percutaneous mitral balloon valvotomy. Restenosis was defined as a decrease in mitral valve area from > or = 1.5 cm2 following percutaneous mitral balloon valvotomy to < 1.5 cm2. There was 80 +/- 4% event-free survival 4 years after percutaneous mitral balloon valvotomy. Multivariate analysis showed chronic atrial fibrillation at baseline (P = 0.039, relative risk (RR) = 2.5) and a high residual maximal gradient after percutaneous mitral balloon valvotomy (P = 0.004, RR = 2.0 per 5 mmHg) to be independent predictors of an event during follow-up. The restenosis rate was 28.3% after 4 years. Chronic atrial fibrillation at baseline (P = 0.0338, RR = 2.2), a small mitral valve area after percutaneous mitral balloon valvotomy (P = 0.0003, RR = 0.8/0.1 cm2) and a high residual maximal transmitral gradient (P = 0.0252, RR = 1.6/5 mmHg) were all independent predictors of restenosis. CONCLUSION: Patients with chronic atrial fibrillation and a high maximal transmitral gradient after percutaneous mitral balloon valvotomy have a higher risk for events during follow-up. Restenosis is related to the presence of chronic atrial fibrillation at baseline and a suboptimal percutaneous mitral balloon valvotomy result.

Importance of basic residues in the nucleocapsid sequence for retrovirus Gag assembly and complementation rescue.

The Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV) contain small interaction (I) domains within their nucleocapsid (NC) sequences. These overlap the zinc finger motifs and function to provide the proper density to viral particles. There are two zinc fingers and at least two I domains within these Gag proteins. To more thoroughly characterize the important sequence features and properties of I domains, we analyzed Gag proteins that contain one or no zinc finger motifs. Chimeric proteins containing the amino-terminal half of RSV Gag and various portions of the carboxy terminus of murine leukemia virus (MLV) (containing one zinc finger) Gag had only one I domain, whereas similar chimeras with human foamy virus (HFV) (containing no zinc fingers) Gag had at least two. Mutational analysis of the MLV NC sequence and inspection of I domain sequences within the zinc-fingerless C terminus of HFV Gag suggested that clusters of basic residues, but not the zinc finger motif residues themselves, are required for the formation of particles of proper density. In support of this, a simple string of strongly basic residues was found to be able to substitute for the RSV I domains. We also explored the possibility that differences in I domains (e.g., their number) account for differences in the ability of Gag proteins to be rescued into particles when they are unable to bind to membranes. Previously published experiments have shown that such membrane-binding mutants of RSV and HIV (two I domains) can be rescued but that those of MLV (one I domain) cannot. Complementation rescue experiments with RSV-MLV chimeras now map this difference to the NC sequence of MLV. Importantly, the same RSV-MLV chimeras could be rescued by complementation when the block to budding was after, rather than before, transport to the membrane. These results suggest that MLV Gag molecules begin to interact at a much later time after synthesis than those of RSV and HIV.

Stenting of "unprotected" left main coronary artery stenoses: early and late results.

OBJECTIVE: To assess short and long term efficacy of coronary stent implantation for unprotected left main coronary artery stenosis. DESIGN: Retrospective follow up study. SETTING: Tertiary referral centre for interventional cardiology and cardiac surgery. PATIENTS: Eighteen consecutive patients (12 men; age 70.8 years) between May 1993 and July 1996. Ten patients presented with stable angina and underwent the procedure electively, eight patients presented either with unstable angina or myocardial infarction and underwent the procedure in emergency. INTERVENTION: Johnson and Johnson Palmaz-Schatz stents were used in 16 patients, and a Microstent and a Gianturco-Roubin in one patient each. An intra-aortic balloon pump was prophylactively used for two patients in the elective group. In the acute group, six required an intra-aortic balloon pump. MAIN OUTCOME MEASURES: Procedural success rate and major adverse cardiac events. RESULTS: Successful stent implantation was achieved in all patients. In the elective group, no major adverse cardiac event occurred during the procedure, but one patient had to undergo repeated angioplasty before discharge. All patients of the elective group were discharged alive and there has been one non-cardiac death during a follow up of (mean (SD)) 10 (4) months. In the emergency group, one patient died during the procedure, one patient developed a non Q-wave myocardial infarction, one patient underwent emergency coronary bypass surgery, while another patient died suddenly before hospital discharge. Six patients of the emergency group were discharged alive and there has been one non-cardiac death during a follow up of 7 (4) months. CONCLUSIONS: Elective stent implantation for unprotected left main coronary artery stenosis is safe and effective in selected stable patients. Urgent stent implantation, however, cannot be considered as a definitive procedure in emergency situation.

Primary coronary stenting after successful balloon angioplasty of chronic total occlusions: a single-center experience.

Coronary angioplasty of chronic total occlusions has been limited by a relatively low success rate and a high average restenosis rate of 53%. We prospectively assessed the immediate and long-term outcome of primary stenting after performing successful recanalization of chronic total occlusions in 38 consecutive patients. Thirty-three men and five women (mean age 56+/-11 years) in whom 39 total occlusions were stented with a successful stent delivery of 97% were evaluated. After stent deployment quantitative angiography demonstrated the mean reference diameter to be 3.42+/-0.44 mm with a mean residual stenosis of 6%+/-9%. Immediately after the stent was implanted, no major complications occurred. Patients underwent clinical and angiographic follow-up at a mean of 6+/-1 months after stent implantation. At 6 months after stent implantation 74% of the patients had no symptoms and remained free of death, myocardial infarction, or target lesion revascularization. Quantitative follow-up angiography was performed in 90% of the patients. The angiographic restenosis rate (>50% diameter stenosis) was 40% (14 of 35 lesions). In eight (23%) of these lesions a reocclusion was noted. Repeat uneventful angioplasty was performed in five (14%) patients with symptomatic restenosis at the stent site, and two (5%) patients had elective coronary artery bypass graft surgery. In conclusion, intracoronary stent implantation is a safe and effective technique in patients with chronic total coronary occlusions. The angiographic restenosis rate of 40% after stenting compares favorably with that in historical balloon angioplasty control series. However, further improvement of this technique is required to reduce the relatively high restenosis rate in patients with chronic total occlusions.

Progression of atherosclerosis after venous coronary artery bypass graft surgery: a 15-year follow-up study.

We investigated the influence of progression of atherosclerosis on clinical outcome in a cohort of 428 consecutive patients with isolated venous coronary artery bypass graft surgery followed prospectively for 15 years. In 189 patients 307 repeat coronary angiograms were performed because of recurrent signs of ischemia. Progression in the native coronary circulation only was found in 38 angiograms (12%), in both the native circulation and in venous grafts in 66 angiograms (21%), in venous grafts only in 135 angiograms (44%), and no progression was found in 68 angiograms (22%). In all the angiographies with a proven progression in the native coronary arteries, 40% was found to be distal to a vein graft insertion. In multivariate analysis the number of distal anastomoses predicts progression in both the native circulation and in venous grafts. Thus, progression is determined by the extensiveness of coronary artery disease at operation. Also, the interval between operation and repeat angiography predicts progression in the native circulation. We conclude that clinical outcome is also determined by progression in the native coronary circulation. Secondary prevention may, therefore, benefit not only the long-term result in patients with venous bypass grafts but probably also in patients with any type of coronary bypass surgery.

Allograft aortic root replacement in prosthetic aortic valve endocarditis: a review of 32 patients.

BACKGROUND: This study was conducted to evaluate allograft aortic root replacement in the setting of complicated prosthetic valve endocarditis with extensive annular destruction. METHODS: From January 1990 through March 1996, 32 patients diagnosed with complicated prosthetic valve endocarditis underwent allograft root replacement. Mean age was 58.3 +/- 13.2 years; 23 patients were men. Mean preoperative New York Heart Association functional class was 3.4. Staphylococcus epidermidis (50%) and Enterococcus faecalis (19%) were the predominant causative microorganisms. Annular abscesses were found in 26 patients (81%), aortic-mitral discontinuity in 14 patients (43%), and left ventricular-aortic discontinuity in 11 patients (34%). A cryopreserved allograft was used in 31 patients (97%) and a fresh antibiotic-treated allograft was used in 1 patient (3%). Mean aortic cross-clamp time was 150 +/- 29 minutes. Mean duration of the postoperative antibiotic treatment was 38.5 +/- 11.8 days. RESULTS: There were three operative deaths (9.4%); causes of death were multiorgan failure in 2 patients (6.2%) and low cardiac output in 1 patient (3.2%). Six patients (18%) had complete heart block (4 patients already before the operation), 3 patients (9.4%) had temporary respiratory insufficiency, and 1 patient (3.2%) needed temporary hemodialysis. Mean follow-up was 37.4 +/- 22.4 months. Two late deaths occurred: 1 patient had recurrent endocarditis, leading to a false aneurysm, and died at reoperation; another patient died of lung cancer. Actuarial 5-year survival was 87.3% (70% confidence interval, 76.8% to 97.8%); actuarial 5-year freedom from recurrent endocarditis was 96.5% (70% confidence interval, 90.0% to 100%). CONCLUSIONS: Allograft aortic root replacement is a valuable technique in the complex setting of prosthetic valve endocarditis with involvement of the periannular region. Mortality and morbidity are low.