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Biomedical subjects

Freek W A Verheugt

Publications and source records attributed to Freek W A Verheugt.

At least 19 recordsLinked to original sources
PubMed2007

Antiplatelet therapy and progression of coronary artery disease: a placebo-controlled trial with angiographic and clinical follow-up after myocardial infarction.

INTRODUCTION: In patients after ST-elevation myocardial infarction (STEMI), antiplatelet therapy reduces subsequent cardiac events, which are often attributed to recurrent thrombosis with (sub)total occlusion in the infarct-related artery. Whether antiplatelet therapy influences the often subclinical process of coronary disease progression in noninfarct arteries has not been reported. METHODS: Quantitative coronary angiography of noninfarct arteries was performed on paired cine-angiograms of 149 patients from fibrinolytic trials who had a patent infarct-related artery 3 to 4 weeks following STEMI and who were randomized to either continue the daily combination of 50-mg aspirin and 400-mg dipyridamole or to matching placebo. Follow-up angiography was scheduled at 1 year. RESULTS: On a per-patient basis, the change in minimal luminal diameter (MLD) was 0.00 mm in the aspirin/dipyridamole group (n = 76) and was 0.01 mm in the placebo group (n = 73). There was no difference between these groups in the changes in MLD (-0.02 mm; 95% CI -0.09 to 0.05), neither were there significant differences in mean luminal diameter and diameter stenosis. Progression (1 segment/patient with > or = 0.40 mm decrease in MLD) was seen in two thirds of patients and did not independently predict long-term death and/or reinfarction. CONCLUSION: In this placebo-controlled trial after STEMI, the combination of aspirin and dipyridamole did not affect noninfarct artery disease progression. Progression did not predict long-term clinical outcome.

Aspirin↗
PubMed2006

Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation acute myocardial infarction: a substudy of the randomized double blind CLARITY-TIMI 28 trial.

BACKGROUND: Fibrinolytic therapy for acute ST-elevation myocardial infarction (STEMI) is frequently limited by delays in administration and by incomplete reperfusion or reocclusion of the infarct-related artery. Intensified prehospital management of STEMI may shorten time to treatment and improve outcomes. METHODS: We carried out a prospective substudy in 11 ambulance systems in 216 of the 3,491 patients with STEMI who were enrolled in the CLARITY-TIMI 28 trial. They were randomized in the ambulance to clopidogrel (n = 109) or placebo (n = 107) along with fibrinolysis, aspirin, and heparin. The primary endpoint was the composite of an occluded infarct-related artery (TIMI flow grade 0 or 1), or death or recurrent myocardial infarction before angiography. RESULTS: All patients received a fibrin-specific lytic and the baseline characteristics in both groups were comparable. The incidence of the primary endpoint was 16.5% in the clopidogrel-treated and 27.1% in the placebo patients (adj OR 0.62, 95% CI 0.31-1.21, p = 0.16), an effect that was consistent with the effects seen in the in-hospital patients in the main CLARITY-TIMI 28 trial. Prehospital clopidogrel therapy reduced the incidence of an occluded infarct-related artery on the predischarge angiogram (11.8% vs. 22.3%, adj OR 0.52, 95% CI 0.24-1.13, p = 0.10). The 30-day incidence of cardiovascular death, recurrent MI or recurrent myocardial ischemia requiring urgent revascularization was 12.8% vs. 14.0% (adj OR 1.07, 95% CI 0.48-2.39, p = 0.87). Early TIMI major bleeding occurred in no clopidogrel patients compared with two placebo patients (1.9%). CONCLUSIONS: Addition of clopidogrel to medical reperfusion of STEMI with fibrinolysis, heparin, and aspirin before reaching the hospital is feasible in medically equipped ambulances without an apparent increase in bleeding. Furthermore, prehospital clopidogrel tended to show better early coronary patency compared to placebo, a result consistent with that observed in patients randomized in-hospital in the CLARITY-TIMI 28 trial.

Aged↗
PubMed2006

Familial sudden death is an important risk factor for primary ventricular fibrillation: a case-control study in acute myocardial infarction patients.

BACKGROUND: Primary ventricular fibrillation (VF) accounts for the majority of deaths during the acute phase of myocardial infarction. Identification of patients at risk for primary VF remains very poor. METHODS AND RESULTS: We performed a case-control study in patients with a first ST-elevation myocardial infarction (STEMI) to identify independent risk factors for primary VF. A total of 330 primary VF survivors (cases) and 372 controls were included; patients with earlier infarcts or signs of structural heart disease were excluded. Baseline characteristics, including age, gender, drug use, and ECG parameters registered well before the index infarction, as well as medical history, were not different. Infarct size and location, culprit coronary artery, and presence of multivessel disease were similar between groups. Analysis of ECGs performed at hospital admission for the index STEMI revealed that cumulative ST deviation was significantly higher among cases (OR per 10-mm ST deviation 1.59, 95% CI 1.25 to 2.02). Analysis of medical histories among parents and siblings showed that the prevalence of cardiovascular disease was similar between cases and controls (73.1% and 73.0%, respectively); however, familial sudden death occurred significantly more frequently among cases than controls (43.1% and 25.1%, respectively; OR 2.72, 95% CI 1.84 to 4.03). CONCLUSIONS: In a population of STEMI patients, the risk of primary VF is determined by cumulative ST deviation and family history of sudden death.

Adult↗
PubMed2006

Hyperhomocysteinaemia and vitamin B12 deficiency: the long-term effects in cardiovascular disease.

BACKGROUND: An elevated plasma homocysteine level is an established risk factor for cardiovascular disease. Vitamin B12 plays a key role in homocysteine metabolism and could be the main factor in causing cardiovascular disease as well. OBJECTIVES: The aim of this study was to assess whether vitamin B12 deficiency or hyperhomocysteinaemia is associated with recurrent cardiovascular events. METHODS: Overall, 211 patients discharged alive from our Coronary Care Unit were recruited from February till May 1998. Serum vitamin B12 and plasma homocysteine levels were measured in fasting blood samples. Patient characteristics, medical information and cardiovascular risk factors were assessed from medical files. Patients were followed for 5 years and the prevalence of cardiovascular mortality and morbidity was collected. RESULTS: In the follow-up period of 810 person-years, 48 (21%) of the patients experienced a nonfatal recurrent cardiovascular event and another 14 (7%) died of a cardiovascular cause. Among those with ischaemic heart disease at discharge, no difference in survival was found between the patients with a low (<250 pmol/l) or a high vitamin B12 level (p = 0.21). In patients with hyperhomocysteinaemia (>16 micromol/l), an increased risk of a recurrent cardio vascular event (p = 0.05) in comparison to those with normal plasma homocysteine levels was proven (adjusted hazard ratio of 2.22 (95% CI: 1.40-3.04). CONCLUSIONS: In conclusion, high plasma homocysteine concentration, but not a low serum vitamin B12 concentration, increases the risk of cardiovascular morbidity and mortality in patients with ischaemic heart disease.

Aged↗
PubMed2006

Aborted myocardial infarction: a new target for reperfusion therapy.

Reperfusion therapy for ST-elevation acute coronary syndromes aims at early and complete recanalization of the infarct-related artery in order to salvage myocardium and improve both early and late clinical outcomes. Myocardial necrosis is usually confirmed and quantified by myocardial enzyme release in plasma. However, over 10% of patients treated with reperfusion therapy fail to develop an enzyme rise, but do exhibit transient ECG changes, which are consistent with an aborted myocardial infarction. The earlier the reperfusion therapy is instituted, the higher the incidence of aborted infarction. Treatment within an hour after symptom onset may result in 25% of aborted infarction and is in combination with complete (70%) ST-segment resolution associated with better survival. This endpoint is easy to define and occurs promptly in time. The faster that effective treatment is initiated, the more likely aborted infarction will occur. Given that mortality, re-infarction, and stroke are declining in incidence, we suggest the introduction of aborted infarction as an endpoint in clinical trials of ST-elevation acute coronary syndromes.

Emergency Treatment↗
PubMed2006

Estimated creatinine clearance instead of plasma creatinine level as prognostic test for postoperative renal function in patients undergoing coronary artery bypass surgery.

BACKGROUND: Preoperative renal failure is a risk factor for adverse events in cardiac surgery. Serum creatinine (SCr) is the most used test for renal failure. However, patients can have significantly decreased glomerular filtration rates with normal SCr levels. More accurate approximation of renal function can be obtained using the Cockroft-Gault equation to calculate an estimated creatinine clearance (CrCl) rate from SCr. METHODS: This study included 627 patients undergoing an isolated CABG between January 2003 and September 2004. CrCl was calculated using the Cockroft-Gault formula. Patients were divided in group A-SCr, 576 patients (91.1%) with a good renal function, SCr < or =1.20 mg/dL for women and < or =1.40 mg/dL for men, and a group B-SCr, with impaired renal function, 51 patients (8.1%). CrCl < or = 50 mL/min was chosen to reflect renal impairment. Group A-CrCl (555 patients, 88.5%) had a normal renal function and group B-CrCl (72 patients,11.5%) an impaired renal function. The studied outcomes were hospital mortality, hospital morbidity, and postoperative renal failure. RESULTS: There was no statistical significant difference between A-SCr and B-SCr group according to the studied outcomes. On the contrary, using the CrCl there was a statistical significant difference between A-CrCl and B-CrCl for the percentage of postoperative renal failure 10 patients (1.8%) versus 5 patients (6.9%) (p=0.00), hospital morbidity 75 patients (13.5%) versus 16 patients (22.2%) (p=0.04). Hospital mortality, 11 patients (2%) versus 4 patients (5.6%), was not significantly (p=0.06) different. Postoperative dialysis, four patients (0.7%) versus three patients (4.2%) (p=0.00), stroke, three patients (0.5%) versus three patients (4.2%) (p=0.00), and hospital stay (7.6 days vs 11.0 days) (p=0.01) were significantly different. CONCLUSION: This study documents that the association between preoperative renal failure and adverse outcomes after CABG is stronger with the estimated CrCl than with the routinely used SCr. Routine estimation or measurement of glomerular filtration rate should be preferred to SCr as screening method for the detection of higher risk patients undergoing CABG.

Acute Kidney Injury↗
PubMed2006

Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis.

The present study was designed to determine whether cardiac inflammation is important for the successful homing of stem cells to the heart after intravenous injection in a murine myocarditis model. Male Bagg albino/c mice were infected with encephalomyocarditis virus (EMCV) to produce myocarditis. Subgroups of mice received single injections by tail vein of embryonic stem cells (ESCs) transfected with green fluorescent protein (GFP) as a marker at days 3, 14, or 60 after infection; other subgroups without stem cell injections were killed at each of these time points to assess the degree of inflammation present. The surviving mice were killed at day 90 after virus infection and hemodynamics, gross pathology, histology, and inflammatory cytokine production in the hearts were measured. Our results indicate that myocardial inflammation was most severe and cytokine production highest at day 14 after EMCV inoculation, and in particular, was strongly positive for interleukin 6. Mice receiving intravenous ESC injections on day 14 after EMCV inoculation showed the largest number of GFP-positive cells at the time of death and the greatest functional improvement compared to uninfected controls without inflammation. We conclude that factors released from myocardium during inflammation are important for enhancing the homing, migration, and implantation of systemically infused stem cells.

Animals↗
PubMed2006

Transport for abciximab facilitated primary angioplasty versus on-site thrombolysis with a liberal rescue policy: the randomised Holland Infarction Study (HIS).

AIMS: As of to date, the only large transportation trial comparing on-site fibrin-specific thrombolysis with transfer for primary angioplasty in patients presenting in a referral centre is the DANAMI-2 trial, with only 3% rescue angioplasty. The Holland Infarction Study (HIS) compared abciximab facilitated primary angioplasty (FP) with on-site fibrin-specific thrombolytic therapy (TT) with a liberal protocol-driven rescue angioplasty (transport to intervention centre in case < 50% ST resolution at 60 min). METHODS AND RESULTS: Patients in a referral centre without shock and < 4.5 h of chest pain presenting with ST-elevation having > or = 12 mm ST-segment shift were randomised to either strategy. Of the originally planned 900 patients only 48 were included due to suspension of financial funding. Death, recurrent MI and stroke at one year was 8% for the FP-group and 22% for the TT-group (p = 0.2). Two hours after randomisation the rates of complete ST-segment resolution (> or =70%) were 52% and 35%, respectively (p = 0.2). CONCLUSION: This prematurely discontinued randomised transportation trial shows favorable trends with respect to long-term clinical outcome and early ST-resolution for abciximab facilitated primary angioplasty. In view of the real world delays associated with interhospital transport for primary angioplasty, treatment strategies focusing on early fibrin-specific lysis with a liberal selective rescue policy are warranted.

Abciximab↗
PubMed2006

Detection of elevated pulmonary capillary wedge pressure in elderly patients with various cardiac disorders by the Valsalva manoeuvre.

In the present study, we assessed whether elevated (> or =15 mmHg) PCWP (pulmonary capillary wedge pressure) can be detected using the blood pressure response to the Valsalva manoeuvre in a group of elderly patients with various cardiac disorders, including atrial fibrillation and valvular heart disease, and healthy elderly controls. The Valsalva manoeuvre was performed in 93 patients (71+/-4 years) and 28 healthy controls (70+/-4 years) undergoing right-sided cardiac catheterization. Blood pressure was measured non-invasively with Finapres. PPR (pulse pressure ratio), the ratio of minimum pulse pressure during phase 2 and maximum pulse pressure during phase 1 of the Valsalva manoeuvre, was correlated with PCWP (r=0.63, P<0.001). The area under the receiver operator characteristic curve of PPR with elevated PCWP was 0.85 (P<0.001). For PPR=0.62, sensitivity for elevated PCWP was 80%, specificity was 79%, positive predictive value was 76% and negative predictive value was 83%. Correlation of PPR with PCWP and the ability of PPR to detect elevated PCWP was present in atrial fibrillation, heart failure and valvular heart disease. In conclusion, PPR is a sensitive and specific instrument to diagnose elevated PCWP non-invasively in a large group of elderly patients with various cardiac disorders. This makes the Valsalva manoeuvre a useful non-invasive tool for diagnosing heart failure, applicable in elderly patients with common cardiac disorders, such as atrial fibrillation and valvular heart disease.

Aged↗