Outcome of transcatheter aortic valve replacement in patients over 85 years of age versus patients aged 85 and younger.

INTRODUCTION: The Dutch general population is aging rapidly. Many of these patient are fit and eligible for TAVR. However, studies on outcome in older versus younger patients are scant. MATERIAL AND METHODS: A single-centre retrospective study comparing patients older and younger than age 85 on outcome. RESULTS: 190 patients underwent TAVR: 136 were aged 85 or younger (U85), 54 were older than 85 (O85). The U85 group had more men (U85: 71 [52.2%] vs O85: 19 [35.2%]; p = 0.034), a higher incidence of diabetes (U85: 36 [26.5%] vs O85: 3 [5.6%]; p = 0.001) and atrial fibrillation (U85: 35 [25.7%] vs O85: 5 [9.3%]; p = 0.03) and a higher body mass index (U85: 27.5 [±â€¯5.24] vs O85: 26 [±â€¯3.78]; p = 0.027). In the O85 group there was a lower estimated glomerular filtration rate (O85: 50.28 [±â€¯15.32] ml/min vs U85: 65.25 [±â€¯29.97] ml/min; p = 0.012). There was no difference in 30-day mortality (U85: 6 [4.4%] vs O85: 3 [5.6%]) and 1­year mortality (U85 9 [6.6%] vs O85 3 [5.6%]) (p = 0.521). There was an equal amount of new onset permanent left bundle branch block (U85: 38 [27.9%] vs O85: 14 [25.9%]; p = 0.896) and permanent pacemaker implantation (U85: 28 [20.6%] vs O85: 28 [20.6%]; p = 0.748). There was no difference in bleeding events (p = 0.469), vascular complications (p = 0.195) or moderate/severe regurgitation (p = 0.972). The U85 group had a slightly longer admission duration (U85 6.29 [±â€¯5.289] days vs O85 5.98 [±â€¯3.328] days (p = 0.037)). CONCLUSION: TAVR in patients over 85 years of age has excellent outcome, comparable to those aged 85 and younger.

Prophylactic veno-arterial extracorporeal membrane oxygenation in patients undergoing high-risk percutaneous coronary intervention.

PURPOSE: Complex high-risk percutaneous coronary intervention (PCI) is challenging and frequently accompanied by haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide cardiopulmonary support in high-risk PCI. However, the outcome is unclear. METHODS: A two-centre, retrospective study was performed of all patients undergoing high-risk PCI and receiving VA-ECMO for cardiopulmonary support. RESULTS: A total of 14 patients (92% male, median age 69 (53-83) years), of whom 50% had previous coronary artery disease in the form of a coronary artery bypass graft (36%) and a PCI (14%) underwent high-risk PCI and received VA-ECMO support. The main target lesion was a left main coronary artery in 78%, a left anterior descending artery in 14%, a right coronary artery in 7%, and 71% underwent multi-vessel PCI in addition to main target vessel PCI. The median SYNTAX score was 27.2 (8-42.5) and in 64% (9/14) there was a chronic total occlusion. Left ventricular function was mildly impaired in 7% (1/14), moderately impaired in 14% (2/14) and severely impaired in 64% (9/14). Cannulation was femoral-femoral in all patients. Median ECMO run was 2.57 h (1-4). Survival was 93% (13/14). One patient died during hospitalisation due to refractory cardiac failure. All other patients survived to discharge. Complications occurred in 14% (2/14), with one patient developing a transient ischaemic attack post-ECMO and one patient developing a thrombus in the femoral vein used for ECMO cannulation. CONCLUSION: VA-ECMO in high-risk PCI is feasible with a good outcome. It can be successfully used for cardiopulmonary support in selected patients.

Pregnancy-related myocardial infarction.

INTRODUCTION: The risk of acute myocardial infarction in young women is low, but increases during pregnancy due to the physiological changes in pregnancy, including hypercoagulability. Ischaemic heart disease during pregnancy is not only associated with increased maternal morbidity and mortality, but also with high neonatal complications. Advancing maternal age and other risk factors for cardiovascular diseases may further increase the risk of ischaemic heart disease in young women. METHODS: We searched the coronary angiography database of a Dutch teaching hospital to identify women with acute myocardial infarction who presented during pregnancy or postpartum between 2011 and 2013. RESULTS: We found two cases. Both women were in their early thirties and both suffered from myocardial infarction in the postpartum period. Acute myocardial infarction was due to coronary stenotic occlusion in one patient and due to coronary artery dissection in the other patient. Coronary artery dissection is a relatively frequent cause of myocardial infarction during pregnancy. Both women were treated by percutaneous coronary intervention and survived. CONCLUSION: Physicians should be aware of the increased risk of myocardial infarction when encountering pregnant or postpartum women presenting with chest pain.

Current MitraClip experience, safety and feasibility in the Netherlands.

PURPOSE: Data on MitraClip procedural safety and efficacy in the Netherlands are scarce. We aim to provide an overview of the Dutch MitraClip experience. METHODS: We pooled anonymised demographic and procedural data of 1151 consecutive MitraClip patients, from 13 Dutch hospitals. Data was collected by product specialists in collaboration with local operators. Effect on mitral regurgitation was intra-procedurally assessed by transoesophageal echocardiography. Technical success and device success were defined according to modified definitions of the Mitral Valve Academic Research Consortium (MVARC). RESULTS: Median age was 76 (interquartile range 69-82) years and 59% were males. Patients presented with ≥moderate mitral regurgitation and a predominance of functional mitral regurgitation (72%). Overall, 611 (53%) patients were treated with one Clip, 486 (42%) with ≥2 Clips and 54 (5%) received no Clip. The number of patients with ≥2 Clips increased from 22% in 2009 to 52% in 2016. Device success and technical success were 91 and 95%, respectively, and were consistent over the years. Significant reduction of mitral regurgitation by MitraClip was achieved in 94% of patients and was observed more often in patients with functional mitral regurgitation (95% vs. 91%, p = 0.025). Device time declined from 145 min in 2009 to 55 min in 2016. CONCLUSION: MitraClip experience in the Netherlands is growing with excellent technical success and device success. Over the years, device time decreased and more patients were treated with ≥2 Clips.

Everolimus- and sirolimus-eluting stents in patients with and without ST-segment elevation myocardial infarction.

AIMS: Everolimus-eluting stents (EES) were superior to sirolimus-eluting stents (SES) in a dedicated myocardial infarction trial, a finding that was not observed in trials with low percentages of ST-elevation myocardial infarction (STEMI). Therefore, this study sought to investigate the influence of clinical presentation on outcome after EES and SES implantation. METHODS: A pooled population of 1602 randomised patients was formed from XAMI (acute MI trial) and APPENDIX-AMI (all-comer trial). Primary outcome was cardiac mortality, MI and target vessel revascularisation at 2 years. Secondary endpoints included definite/probable stent thrombosis (ST). Adjustment was done using Cox regression. RESULTS: In total, 902 EES and 700 SES patients were included, of which 44 % STEMI patients (EES 455; SES 257) and 56 % without STEMI (EES 447; SES 443). In the pooled population, EES and SES showed similar outcomes during follow-up. Moreover, no differences in the endpoints were observed after stratification according to presentation. Although a trend toward reduced early definite/probable ST was observed in EES compared with SES in STEMI patients, long-term ST rates were low and comparable. CONCLUSIONS: EES and SES showed a similar outcome during 2-year follow-up, regardless of clinical presentation. Long-term safety was excellent for both devices, despite wide inclusion criteria and a large sub-population of STEMI patients.

Treatment of Aortic Stenosis With a Self-Expanding, Resheathable Transcatheter Valve: One-Year Results of the International Multicenter Portico Transcatheter Aortic Valve Implantation System Study.

BACKGROUND: The aim of the Portico TAVI (transcatheter aortic valve implantation) system study was to evaluate outcomes ≤1 year after implantation of a novel resheathable, self-expanding TAVI system in a multicenter patient population with severe aortic stenosis (AS). METHODS AND RESULTS: High-risk patients (n=222) with symptomatic severe AS (mean age, 83.0±4.6 years; 74.3% women) were enrolled across 12 centers in Europe and Australia. The study's primary end point was all-cause mortality at 30 days. A total of 209 patients who received the Portico TAVI system were available for follow-up after the 30-day visit. Data collection included hemodynamic assessment by echocardiography with core laboratory evaluation and assessment of functional status. Valve Academic Research Consortium-defined adverse events were adjudicated by an independent Clinical Events Committee. TAVI using the Portico valve led to a significant and persistent improvement in aortic valve function at 1 year. More than mild paravalvular leak was present in 5.7% and 7.5% of patients at 30 days and 1 year, respectively. Kaplan-Meier estimates at 30 days and 1 year were 3.6% and 13.8% for all-cause mortality, 3.6% and 9.6% for cardiovascular mortality, and 3.2% and 5.8% for major (disabling) stroke. After 30 days and ≤1 year of follow-up, adverse events included stage 3 acute kidney injury (n=3), major vascular complications (n=5), and life-threatening/disabling bleeding (n=3). Overall permanent pacemaker rate was 14.7%. At 1 year, 74.8% improved ≥1 New York Heart Association class compared with baseline (P<0.0001). CONCLUSIONS: The Portico TAVI system is safe and effective at 1 year, yielding low mortality and stroke rates in high-risk patients with severe AS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01493284.

Lipoprotein lipase activity is associated with severity of angina pectoris. REGRESS Study Group.

BACKGROUND: Raised triglyceride-rich lipoproteins significantly increase the risk for cardiovascular disease. Variation in the activity of the enzyme lipoprotein lipase (LPL), which is crucial in the removal of these lipoproteins, may therefore modulate this risk. METHODS AND RESULTS: Postheparin levels of LPL activity and mass were measured in a large cohort of male coronary artery disease patients participating in the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering regression trial. In addition, the relationships between LPL activity and mass and severity of angina pectoris according to the NYHA classification and silent ischemia on 24-hour ambulatory ECG monitoring were assessed. Patients in different LPL activity quartiles and mass had different severities of angina; a total of 47% of patients in the lowest LPL quartile reported class III or IV angina. In contrast, only 29% in the highest activity quartile (P:=0.002) had severe angina. These parameters were supported by ambulatory ECG results, for which the total ischemic burden in the lowest LPL activity quartile was 36. 5+/-104.1 mm x min compared with 14.8+/-38.8 mm x min in the highest quartile of LPL activity (P:=0.001). LPL activity levels were strongly correlated with LPL mass (r=0.70, P:<0.0001). A significant association between the LPL protein mass and NYHA class (P:=0.012) was also demonstrated. CONCLUSIONS: We have demonstrated a significant relationship between LPL mass and activity and severity of ischemia as defined by angina class and ambulatory ECG. These results suggest that LPL influences risk for coronary artery disease by both catalytic and noncatalytic mechanisms.

No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium.

OBJECTIVES: We sought to prospectively compare nitrogen-13 (13N)-ammonia/18fluorodeoxyglucose (18FDG) positron emission tomography (PET)-guided management with stress/rest technetium-99m (99mTc)-sestamibi single-photon emission computed tomography (SPECT)-guided management. BACKGROUND: Patients with evidence of jeopardized (i.e., ischemic or viable) myocardium may benefit from revascularization, whereas patients without it should be treated with drugs. Both PET and SPECT imaging have been proven to delineate jeopardized myocardium. When patient management is based on identification of jeopardized myocardium, it is unknown which technique is most accurate for long-term prognosis. METHODS: In a clinical setting, 103 patients considered for revascularization with left ventricular wall motion abnormalities and suspicion of jeopardized myocardium underwent both PET and SPECT imaging. The imaging results were used in a randomized fashion to determine management (percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass graft surgery [CABG] or drug treatment). Follow-up for cardiac events (cardiac death, myocardial infarction and revascularization) was recorded for 28 +/- 1 months. The study was designed to have a power of 80% to detect a 20% difference in the event rate between PET- and SPECT-based management. RESULTS: Management decisions in 49 patients randomized to PET (12 who had PTCA, 14 CABG and 23 drug therapy) were comparable with 54 patients randomized to SPECT (15 who had PTCA, 13 CABG and 26 drug therapy). In terms of cardiac event-free survival, no differences between PET and SPECT were observed (11 vs. 13 cardiac events for PET and SPECT, respectively; p = NS by the Kaplan-Meier statistic). CONCLUSIONS: No difference in patient management or cardiac event-free survival was demonstrated between management based on 13N-ammonia/18FDG PET and that based on stress/rest 99mTc-sestamibi SPECT imaging. Both techniques may be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Pre-procedural ACE-activity does not predict symptomatic in-stent restenosis.

BACKGROUND: Several studies indicate that ACE-activity is related to atherosclerosis. We investigated the correlation between ACE-activity, in plasma as well as in the atherosclerotic plaque, and in-stent restenosis. METHODS AND RESULTS: ACE-activity was measured in blood samples from 178 patients who underwent a percutaneous coronary intervention with stent placement. During 8 months follow-up, 51 of these patients had an adverse clinical event. ACE-activity did not differ between patients with or without adverse events (21.5 vs. 23.1 nM/ml/min; P=0.36). Tissue samples were obtained with an atherectomy catheter before elective stent placement in another group of 13 patients with de novo stenosis. In this tissue, we determined the ACE-content immunohistologically. These patients were scheduled for follow-up quantitative coronary angiography after 12 months. In this group, the quantity of ACE was not correlated to the late luminal loss (0.31 vs. 0.38 mm; P=0.76). CONCLUSION: In this study, pre-procedural ACE-activity, in plasma as well as in the atherosclerotic plaque, does not predict the occurrence of in-stent restenosis.

Dutch guidelines for interventional cardiology: institutional and operator competence and requirements for training.

Interventional cardiology is an expanding field within cardiovascular medicine and today it is generally accepted that cardiologists require specific training, knowledge and skills. Hospitals where coronary interventions are performed must be properly equipped and able to provide specialised care. Percutaneous coronary interventions are frequently used for coronary revascularisation. The public should have confidence in the uniformity of high quality care. Therefore, such quality of care should be maintained by certification of the individual operators, general guidelines for institutional requirements and formal audits. The Netherlands Society of Cardiology (NVVC) will be implementing a new registration system for cardiologists with a subspecialisation that will include registration for interventional cardiology. The NVVC asked the Working Group of Interventional Cardiology (WIC) to update the 1994 Dutch guidelines on operator and institutional competence, and requirements for training in interventional cardiology in order to incorporate them into the official directives. The present guidelines represent the expert opinion of the Dutch interventional cardiology community and are in accordance with international regulations. After two rounds of discussion, the NVVC approved the guidelines in November 2004 during the autumn meeting.

Effect of pravastatin on progression and regression of coronary atherosclerosis and vessel wall changes in carotid and femoral arteries: a report from the Regression Growth Evaluation Statin Study.

Few data are available about the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels. REGRESS is a double-blind, placebo-controlled, multicenter study to assess the effect of a 2-year treatment with the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis using quantitative coronary arteriography in 885 male patients with a total serum cholesterol value of 155-310 mg/dl (4-8 mmol/liter). Among symptomatic men with significant coronary atherosclerosis and normal to moderately raised levels of serum cholesterol, patients treated with pravastatin had less progression of coronary atherosclerosis and fewer new cardiovascular events than patients in the placebo group. Ultrasound examinations of carotid and femoral arteries were performed in 255 patients. Changes in intimal-medial thickness also showed a treatment effect from pravastatin; however, on a per patient basis, there was no correlation with the treatment effect in the coronary arteries.

Pravastatin reduces restenosis two years after percutaneous transluminal coronary angioplasty (REGRESS trial).

The Regression Growth Evaluation Statin Study (REGRESS) is a placebo-controlled multicenter study designed to assess the effect of 2-year treatment with pravastatin on the progression and regression of angiographically documented coronary artery disease. One of the secondary end points was the occurrence of 2-year restenosis in the percutaneous transluminal coronary angioplasty (PTCA) block. We randomly assigned eligible patients to receive pravastatin 40 mg once daily or placebo. The end point was the percent diameter stenosis of the target lesion at 24 months, as assessed by (semi)quantitative coronary angiography. Two hundred twenty-one patients underwent scheduled PTCA, which was considered successful in 201 patients. One hundred seventy-eight patients underwent angiographic restudy (89%). The patients in the pravastatin group (n = 109) and placebo group (n = 112) were similar at baseline. Percent diameter stenosis before angioplasty was 78 +/- 14% (mean +/- SD) in the pravastatin group and 80 +/- 14% in the placebo group (p = 0.46). At follow-up, the percent diameter stenosis was 32 +/- 23% in the pravastatin group and 45 +/- 29% in the placebo group (p < 0.001). Clinical restenosis was significantly lower in the pravastatin group (7%) compared with the placebo group (29%) (p < 0.001). Risk reduction for all events was 58%. We conclude that treatment with pravastatin reduces 2-year clinical and angiographic restenosis.

Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with fosinopril and pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the Prevention of REnal and Vascular ENdstage Disease Intervention Trial [PREVEND IT]).

This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive (RR <160/100 mm Hg and not using antihypertensive medication) and nonhypercholesterolemic (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid lowering medication) men and women with persistent microalbuminuria (urinary albumin excretion >10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease.

Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis.

It has proved difficult to identify high-risk patients for atherosclerosis and to determine how they might respond to medication. Recently, a common promoter variant of the human stromelysin-1 gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events, especially restenosis and progression of coronary artery disease and whether the effect was modulated by treatment with pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating in the Regression Growth Evaluation Statin Study (REGRESS) study, a clinical trial assessing the effect of the lipid-lowering drug pravastatin on the progression of atherosclerosis. Patients in the placebo group with 5A6A or 6A6A genotypes had more clinical events than patients with the 5A5A genotype (26% and 12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo, whereas it was unchanged in those with a 5A5A genotype (p value for interaction: 0.038). Also, the incidence of repeat angioplasty in the placebo group was greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes (38% and 40%, respectively, vs 11%, p = 0.09). Again, treatment substantially reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%, respectively), whereas it was unchanged in 5A homozygotes (28%, p for interaction: 0.002). These effects were independent of the effects of pravastatin on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter polymorphism confers a genotype-specific response to medication in determining clinical event-free survival and the risk for symptom-driven repeat angioplasty. This variant may therefore act as a predictor, not only of disease progression, but also of response to therapy and risk of restenosis.

The 4S study. Implications for prescribing.

This article discusses various aspects of cholesterol-lowering therapy using the HMG-CoA reductase inhibitor simvastatin in the light of the large Scandinavian Simvastatin Survival Study (4S). In 4S, patients with proven coronary heart disease (CHD) and plasma total cholesterol > 5.5 mmol/L (212 mg/dl) despite dietary measures received statin therapy or placebo for > or = 5 years. A significant mortality reduction was accomplished in those receiving the statin. Moreover, a significant decrease of nonfatal myocardial infarction and requirement for coronary bypass surgery or angioplasty was demonstrated, which will contribute to the cost-effectiveness of this well tolerated therapy. Plaque stabilisation and improvement of endothelial function are thought to be mediators of this therapeutic success. Responsible drug prescription in the post-4S era may result in the recognition and treatment of more patients with CHD. This is likely to be more beneficial than exhaustive efforts to completely achieve the goals of the most strict guidelines in the individual patient. In patients who carry the highest absolute risk for a recurrent event, aggressive drug therapy may be most justified. Reluctance to initiate lipid lowering drug therapy in patients with proven CHD should now be disputed.

Functional integrity and aging of the left internal thoracic artery after coronary artery bypass surgery.

OBJECTIVE: To study the endothelial function in the left internal thoracic artery after coronary artery bypass surgery and to identify predictors of early dysfunction, we performed a provocative test with acetylcholine in 23 male patients who underwent routine postoperative coronary angiography. METHODS: The change in mean diameter of the proximal thoracic artery was assessed by quantitative angiography after selective injections of acetylcholine and nitroglycerin. RESULTS: The thoracic artery showed a 6.8% (P <. 001) and 9.0% (P <.001) increase in mean diameter after acetylcholine and nitroglycerin administration, respectively. Vasodilative responses to acetylcholine and nitroglycerin administration were strongly correlated (R: 0.88; P <.001). Among the common risk factors, only age was associated with an impairment in the vasodilative response of the arterial graft (P =.001), and acetylcholine-induced vasodilation was inversely correlated to the age of the patient (R: 0.69; P <.001). CONCLUSIONS: Endothelium-dependent vasodilative response to acetylcholine administration seems well preserved in the left internal thoracic artery after surgery. Common risk factors, except for age, do not affect the functional integrity of the arterial graft. The vasodilative properties of the graft depend on the age of the patient and do not deteriorate over time after operation.

Lipoprotein(a) levels in patients with myocardial infarction treated with anistreplase: no prediction of efficacy but inverse correlation with plasminogen activation in non-patency.

The aim of this study was to investigate whether failure of thrombolytic treatment might be due to inhibition of fibrinolysis by high lipoprotein(a) levels. Fifty-eight patients with acute myocardial infarction were treated intravenously within 4 h after onset of symptoms with anistreplase (30 units) and heparin (30,000 IU/24 h). Blood samples for measurement of coagulation parameters were taken before and 1.5 h after treatment. Coronary angiography was performed after 48 h. Levels of lipoprotein(a) were measured 6 months after discharge from hospital. The patency rate was 74% (43/58). Median lipoprotein(a) levels were not different between the patients with a patent and those with a non-patent vessel (10 and 8 mg/dl, respectively), however, in patients with a non-patent infarct-related vessel, a significant inverse correlation was found between the lipoprotein(a) level and the decrease of plasminogen in the first 1.5 h after treatment. It is concluded that high lipoprotein(a) levels, although not directly associated with a poor outcome of anistreplase therapy, might contribute to insufficient fibrinolysis in patients with a non-patent infarct-related vessel.

The role of coronary endothelial function testing in patients suspected for angina pectoris.

Coronary vasomotor function plays an important role in onset and progression of coronary artery disease. Suwaidi [Circulation 101 (2000) 948] and Schächinger [Circulation 101 (2000) 1899] demonstrated that vasomotor dysfunction has a significant impact on events in patients with minimal coronary artery disease. Endothelial specific testing can be performed in coronary as well as peripheral arteries. However, non-coronary tests have a low correlation with the coronary vasomotor response, as assessed by acetylcholine. In large clinical prospective placebo-controlled trials, angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering drugs reduce morbidity and mortality after myocardial infarction or myocardial infarction-induced heart failure. The same drugs restore endothelial dysfunction after myocardial infarction, as was demonstrated in small experimental and clinical studies. Recent studies in patients with coronary artery disease showed a relation with endothelial dysfunction and the occurrence of adverse coronary events. For this reason, it is important to develop methods to evaluate endothelial function.

Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial.

BACKGROUND: Folic acid is assumed to have favourable effects on vascular endothelium, directly as well as indirectly through its effect on homocysteine metabolism. However, the clinical value of folic acid in secondary prevention after acute myocardial infarction (MI) has never been tested. Thus, a randomised, open-label, multicentre trial was performed in order to study the effect of folic acid 5 mg o.d. when added to statin therapy on the incidence of recurrent major clinical events up to 1 year post-MI. METHODS: A total of 283 patients with a total cholesterol >6.5 mmol/l (251 mg/dl) (mean 7.3 mmol/l) were included. All patients received 40 fluvastatin. In 140 of the 283 patients, folic acid (5 mg o.d.) was instituted at discharge, and the remaining 143 patients served as controls. Other secondary prevention measures for both groups were advocated. The primary endpoint was a composite consisting of all vascular events, including death, recurrent MI, strokes, and unplanned invasive coronary interventions. RESULTS: At baseline, the two groups were well-matched for all clinical and demographic parameters. After 1 year of treatment, no difference was noticed in the primary endpoint between the two groups. These endpoints occurred in 43 patients (31%) in the folic acid group, as opposed to 45 patients (31%) in the control group. All separate cardiovascular events were also equally distributed between both groups. Total cholesterol levels decreased to a similar extent in the two groups (to 5.5 and 5.7 mmol/l, in folic acid and control groups, respectively). CONCLUSIONS: In this medium-size pilot study, folic acid did not demonstrate any beneficial additive effects on cardiovascular mortality or morbidity in post-MI patients with hypercholesterolemia who were treated with statin therapy. Larger trials, possibly targeting at selected populations, must be awaited before definitive conclusions regarding the potentially favourable effects of folic acid supplementation in secondary prevention can be drawn.

Multilink stent promotes less platelet and leukocyte adhesion than a traditional stainless steel stent: an in vitro experimental study.

BACKGROUND: Platelet and leukocyte deposition onto metallic struts can be a crucial factor in the outcome of a coronary stenting procedure. By means of an in vitro, closed-loop circulation model, we aimed to assess blood-stent interaction patterns for a new stainless steel stent (MultiLink, Guidant Nederland BV, Nieuwegein, the Netherlands). METHODS: The effect of MultiLink (n=20) on blood cells and blood activation was studied by biochemical assays. Platelet and leukocyte adhesion to MultiLink were studied by immunofluorocytometric assays (anti-GpIIIa [CD 61] and anti-CD11b labeled antibodies, respectively), and by scanning electron microscopy. MultiLink was compared with empty circuits (n=20) and to the Palmaz Schatz stent (n=20). Experiments were performed both in the presence and in the absence of an antiplatelet agent (15 microg/mL of indomethacin). RESULTS: No significant effect on blood cells and blood activation was demonstrated for MultiLink. Antiplatelet treatment significantly reduced platelet adhesion to MultiLink (from 3.78+/-1.28 to 2.23+/-0.57 x 10(6) count per second [cps]/stent) but not to the Palmaz Schatz stent (from 4.11+/-0.31 to 5.02+/-1.29 x 10(6) cps/stent)(P=0.011). Leukocyte adhesion to MultiLink was significantly less than adhesion to the Palmaz Schatz stent (7.95+/-1.59 vs. 9.16+/-1.36 x 10(6) cps/stent, respectively; P=0.016), regardless of the presence of antiplatelet treatment. CONCLUSIONS: When compared with a traditional stainless steel stent, MultiLink seems to have features of improved hemocompatibility, and single antiplatelet treatment is proposed as the treatment of choice to prevent platelet deposition.