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Biomedical subjects

F van de Werf

Publications and source records attributed to F van de Werf.

At least 19 recordsLinked to original sources

Fatal prosthetic valve endocarditis due to Campylobacter fetus.

Campylobacter fetus subspecies fetus has a predilection for vascular endothelium. This report describes a case of a prosthetic valve infective endocarditis due to this microorganism. Despite adequate antibiotic combination treatment, valvular vegetations and perivalvular suppurative complications evolved, leading to valvular dysfunction, heart failure and death. Only three other cases of C. fetus prosthetic valve endocarditis have been described previously. Campylobacter fetus bacteraemia must be considered cautiously, because of the risk of late cardiac or vascular complications.

Anti-Bacterial Agents↗

Resolution of ST-segment elevation in acute myocardial infarction--early prognostic significance after thrombolytic therapy. Results from the COBALT trial.

In acute myocardial infarction, early identification of patients at a high mortality risk is important for planning further therapeutic strategies. Previous studies have demonstrated that the extent of early resolution of ST-segment elevation may represent a simple, quick and noninvasive assessment to identify high risk groups of patients. In a subgroup of the COBALT Study population (Continuous Infusion vs Double Bolus Administration of Alteplase), ST-segment elevation was measured before and 90 to 120 minutes after treatment with alteplase. The subgroup of n = 1,760 patients was not different from the total COBALT population of n = 7169 patients regarding most clinical parameters except Killip Class before treatment. However, the overall 30-day mortality differed significantly between the main study and the substudy (7.76% vs 3.52%; p < 0.001). Three groups of ST-segment resolution were defined: 1. complete resolution (resolution > or = 70%; 762 patients), 2. partial resolution (< 70% and > 30%; 491 patients), 3. no resolution (< 30%; 507 patients). Mortality rate at 30 days for complete, partial and no resolution of ST-segment elevation was 1.31%, 4.28% and 6.11%, respectively (p < 0.001). While this significant correlation between the extent of ST-segment resolution and mortality could be observed for inferior acute myocardial infarction, it could not be found in patients with anterior acute myocardial infarction. This in part may be due to a selection bias that leads to an extremely divergent mortality rate of anterior acute myocardial infarction in the main study and the substudy (10.1% vs 3.94%; p < 0.0001). Despite this limitation, resolution of ST-segment elevation in acute myocardial infarction after thrombolytic therapy allows to identify patients at a high mortality risk and may help to select patients for early invasive procedures such as PTCA. Patients with complete ST-segment resolution showed a particularly low mortality rate, irrespective of the alteplase regimen used (front-loaded alteplase vs double bolus alteplase).

Acute Disease↗

Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries.

OBJECTIVES: We assessed the use and effects of acute intravenous and later oral atenolol treatment in a prospectively planned post hoc analysis of the GUSTO-I dataset. BACKGROUND: Early intravenous beta blockade is generally recommended after myocardial infarction, especially for patients with tachycardia and/or hypertension and those without heart failure. METHODS: Besides one of four thrombolytic strategies, patients without hypotension, bradycardia or signs of heart failure were to receive atenolol 5 mg intravenously as soon as possible, another 5 mg intravenously 10 min later and 50 to 100 mg orally daily during hospitalization. We compared the 30-day mortality of patients given no atenolol (n=10,073), any atenolol (n=30,771), any intravenous atenolol (n=18,200), only oral atenolol (n=12,545) and both intravenous and oral drug (n=16,406), after controlling for baseline differences and for early deaths (before oral atenolol could be given). RESULTS: Patients given any atenolol had a lower baseline risk than those not given atenolol. Adjusted 30-day mortality was significantly lower in atenolol-treated patients, but patients treated with intravenous and oral atenolol treatment vs. oral treatment alone were more likely to die (odds ratio, 1.3; 95% confidence interval, 1.0 to 1.5; p=0.02). Subgroups had similar rates of stroke, intracranial hemorrhage and reinfarction, but intravenous atenolol use was associated with more heart failure, shock, recurrent ischemia and pacemaker use than oral atenolol use. CONCLUSIONS: Although atenolol appears to improve outcomes after thrombolysis for myocardial infarction, early intravenous atenolol seems of limited value. The best approach for most patients may be to begin oral atenolol once stable.

Administration, Oral↗

Assessment of myocardial viability in chronic coronary artery disease using technetium-99m sestamibi SPECT. Correlation with histologic and positron emission tomographic studies and functional follow-up.

OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI]) as a viability tracer was investigated in patients undergoing coronary artery bypass graft surgery. BACKGROUND: Initial studies claim that rest MIBI single-photon emission computed tomographic (SPECT) studies can be used to assess myocardial viability. METHODS: Thirty patients with a severely stenosed left anterior descending coronary artery and wall motion abnormalities were prospectively included. The patients underwent a MIBI rest study, a positron emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study and nuclear angiography before undergoing bypass surgery. A preoperative transmural biopsy specimen was taken from the left ventricular anterior wall. Morphometry was performed to assess percent fibrosis. After 3 months, radionuclide angiography was repeated. RESULTS: Statistically significant higher MIBI values were found in the group with myocardial viability as assessed by PET than in the group with PET-assessed nonviability (p < 0.01). Significantly higher MIBI values were found in the group with enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When maximizing the threshold for assessment of viability with MIBI by using functional improvement as the reference standard, a cutoff value of 50% was found, with positive and negative predictive values of 82% and 78%, respectively. CONCLUSIONS: 99mTc MIBI uptake was significantly higher in PET-assessed viable areas and in regions with enhanced contractility at 3 months. A linear relation was found between percent fibrosis and MIBI uptake. An optimal threshold of 50% was found for prediction of functional recovery.

Ammonia↗

Heart rate variability after cardiac transplantation in humans.

The reappearance of cardiac innervation after cardiac transplantation remains a matter of debate. We evaluated the ability of heart rate variability (HRV) analysis to detect the extent and time course of functional cardiac allograft reinnervation. Time- and frequency-domain analysis of heart rate was performed on Holter recordings of 120 heart transplant and four heart-lung transplant recipients. A high frequency (HF) component was clearly distinguished on visual inspection of power spectral density in 42 patients. In eight patients an HF component of normal magnitude was detected. The other 34 patients in this group, including all four heart-lung transplants, presented with a very small HF component. The other 82 patients showed a flat spectrum. The group with an HF component of normal amplitude was significantly different, compared to the other groups, for all HRV parameters. Serial plotting of HRV parameters of the patients with an HF component of normal amplitude against time posttransplant, revealed, from 12 months onwards, a progressive increase of parameters denoting HF variability. In five heart transplant patients with acute allograft rejection, the use of HRV analysis for rejection monitoring was unsuccessful. These results suggest that, inasmuch as the HF component of HRV is caused by parasympathetic cardiac innervation, the HF component of normal amplitude, observed in only a minority of cardiac transplant recipients (6%), is a marker for parasympathetic reinnervation. The evolution over time of this HF component is compatible with a biological phenomenon as gradual parasympathetic reinnervation of the sinus node.

Autonomic Nervous System↗

A pilot study on bolus administration of recombinant staphylokinase for coronary artery thrombolysis.

Recombinant staphylokinase (Sak) is a highly fibrin-specific thrombolytic agent but the optimal dose and mode of administration remain to be defined. Intravenous (i.v.) infusion over 5 min of 20 mg Sak in 12 patients with acute myocardial infarction induced complete coronary patency (TIMI perfusion grade 3) in 7 patients (58%) within 60 min. In 3 of the 5 patients with no or suboptimal flow (TIMI grade 0, 1 or 2) at 60 min, an additional 10 mg i.v. bolus of Sak resulted in TIMI grade 3 flow at 90 min. No major treatment-related complication occurred. Residual fibrinogen and alpha 2-antiplasmin levels at 90 min were 110 +/- 6.0% and 98 +/- 4.1% (mean +/- SEM) of baseline, respectively. Median antibody-related Sak-neutralizing activity was low at baseline (0.0 microgram/ml) and after 1 week (0.5 microgram/ml) but increased from day 10 on (to 4.0 micrograms/ml). Thus, bolus thrombolysis with Sak may induce efficient coronary artery recanalization while preserving circulating fibrinogen and alpha 2-antiplasmin. Comparative trials of coronary thrombolysis with double-bolus Sak appear to be warranted.

Aged↗

Thrombolytic therapy and acute aortic dissection.

Thrombolytic (tissue plasminogen activator) and antithrombotic treatment (heparin and aspirin) were given to a 47-year-old man with an acute type II aortic dissection presenting as an acute anterior myocardial infarction. During treatment he developed cardiac tamponade and an ischaemic stroke. Transoesophageal echocardiography (but not computed tomographies of the chest) revealed the correct diagnosis. After surgical repair (Bentall procedure) there was a complete recovery.

Aortic Dissection↗

Left ventricular function changes during pharmacological and physiological interventions and routine activities monitored in healthy volunteers by a portable radionuclide probe (VEST).

A miniaturized radionuclide cardiac probe incorporated in a semi-rigid plastic chest garment has made ambulatory left ventricular (LV) function evaluation possible, with gated nuclear data being stored on tape together with electrocardiographic data, for subsequent off-line processing. After red blood cell labelling with 555 MBq (15 mCi) 99mTc and standard gated blood pool imaging in 45 degrees LAO, we performed a continuous monitoring of LV function in 20 healthy male volunteers (age range: 22-25 years), in resting control conditions as well as during activities (standing, walking, climbing stairs) and after interventions (isosorbide dinitrate intake, Trendelenburg position, inflation of cuffs around the thighs). VEST-monitoring proved to be a reliable method that gave reproducible results: changes of ejection (EF) in basal conditions were lower than 5% in 95% of the patients. Changes in LV function caused by daily activities were easily demonstrated. While standing effected no significant EF changes, walking and climbing increased EF by 6.9% (p less than 0.05) and 21.2% (p less than 0.05) respectively. Changes in LV volumes caused by alterations in venous return were also demonstrated. Compared with baseline, Trendelenburg increased end-diastolic volume (EDV) by 2.9% while isosorbide dinitrate and inflation of cuffs decreased it by 5.7% and 2.2% respectively.

Adult↗

An expert system for the labeling and 3D reconstruction of the coronary arteries from two projections.

In this paper we present a rule-based expert system for the automatic delineation and 3D reconstruction of the left coronary artery on standard RAO and LAO angiographic projections. The approach is based on the application of a general blood vessel model and on anatomical models which take into account the normal variations of the coronary artery structure. In a first step, the arteries are delineated by detecting the maximum intensity on the centerline of the vessels. Then, we label the blood vessel segments according to an anatomical model of the left coronary artery. In general, only 1-2 labels remain for each blood vessel segment. Finally, these results are used for an automatic 3D reconstruction of the left coronary artery from two projections. Results from clinical RAO and LAO angiograms will be presented.

Algorithms↗

Comparison of angiographic methods for the assessment of the extent of experimental anterior myocardial infarction in dog hearts.

Infarction was provoked in the dog by introducing a copper coil into the left anterior descending coronary artery. Eight groups, each of 6 dogs, were studied which received various treatments and were evaluated after 24 hours or 1 week. The anatomical extent of infarction was measured by the triphenyltetrazoliumhydrochloride method; size was evaluated angiographically by the centerline, chord and radial method and by ejection fraction. The extent of infarction was similar in groups studied after 24 hours and 1 week. Angiographical changes were most marked after 24 hours, and the ejection fraction was related to the extent of infarction (r = -0.5; P less than 0.02). Some parameters of the radial and centerline method showed also a relation to the extent of infarction (r = 0.47 to 0.57; P less than 0.05). After one week, the ejection fraction was no longer correlated to the extent of infarction. The correlation between the parameters of the chord, radius and centerline method and the extent of infarction improved to r-values of 0.58 to 0.63 (P less than or equal to 0.01). There was no difference between the 3 methods.

Adrenergic beta-Antagonists↗

Bolus alteplase.

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Clinical Trials as Topic↗

Long term spontaneous evolution of left ventricular function after experimental acute coronary occlusion.

In a canine model of acute occlusion of the left anterior descending artery (LAD), left ventriculography was performed before and immediately after occlusion and also one and three weeks later. Regional left ventricular function was evaluated by the centreline method. Global and regional left ventricular function were significantly depressed immediately after occlusion and showed no significant recovery after one and three weeks, except for a decrease in the paradoxical motion of the LAD territory, which was probably due to stiffening of the infarct area.

Angiocardiography↗

Pharmacokinetics and thrombolytic properties of a nonglycosylated mutant of human tissue-type plasminogen activator, lacking the finger and growth factor domains, in dogs with copper coil-induced coronary artery thrombosis.

The pharmacokinetics and thrombolytic properties of a variant of human tissue-type plasminogen activator (t-PA), obtained by deletion mutagenesis of the NH2-terminal fibronectin-like finger (F) and epidermal growth factor (E) domains, and substitution of the three known glycosylated Asn residues by Gln (t-PA-delta FE3X), were studied in dogs with a copper coil-induced thrombosis of the left anterior descending coronary artery. Bolus injections were given during 2 min to groups of three dogs. Injection of 0.15 mg/kg resulted in peak antigen levels in plasma of 1.58 +/- 0.72 micrograms/ml (mean +/- SEM) and caused reperfusion within 14 +/- 6 min. With 0.075 mg/kg, corresponding values of 0.81 +/- 0.20 micrograms/ml and 31 +/- 15 min were obtained. A bolus of 0.038 mg/kg yielded plasma peak levels of 0.43 +/- 0.20 micrograms/ml but did not cause coronary recanalization within 3 h. A bolus injection of natural t-PA (Mel-t-PA) at a dose of 0.1 mg/kg in four dogs resulted in plasma peak levels of 0.46 +/- 0.09 micrograms/ml and caused partial coronary artery reperfusion within 3 h in one of four dogs (after 31 min). None of these injections caused a significant decrease of the fibrinogen level. Pharmacokinetic parameters for t-PA-delta FE3X were alpha half-life (t1/2) 14-18 min, beta t1/2 72-125 min, and plasma clearance 21-36 ml/min. For Mel-t-PA, the corresponding values were 3 min, 8 min, and 520 ml/min. We conclude that the variant t-PA-delta FE3X has a markedly longer plasma t1/2 than does Mel-t-PA and, when administered as a bolus injection, a higher thrombolytic efficacy.

Animals↗