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Biomedical subjects

W H Van Gilst

Publications and source records attributed to W H Van Gilst.

At least 19 recordsLinked to original sources
PubMed2003

The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.

BACKGROUND: National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. METHODS: The survey screened discharge summaries of 11304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. CONCLUSION: Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.

Adrenergic beta-Antagonists↗
PubMed2001

Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels.

OBJECTIVES: Our purpose was to determine whether patients with persistent atrial fibrillation (AF) and patients with paroxysmal AF show alterations in potassium channel expression. BACKGROUND: Persistent AF is associated with a sustained shortening of the atrial action potential duration and atrial refractory period. Underlying molecular changes have not been studied in humans. We investigated whether a changed gene expression of specific potassium channels is associated with these changes in patients with persistent AF and in patients with paroxysmal AF. METHODS: Right atrial appendages were obtained from 8 patients with paroxysmal AF, 10 with persistent AF and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass surgery, whereas most AF patients underwent Cox's MAZE surgery (atrial arrhythmia surgery to cure AF) (n = 12). All patients had normal left ventricular function. mRNA (ribonucleic acid) levels were measured by semiquantitative polymerase chain reaction and protein content by Western blotting. RESULTS: mRNA levels of transient outward channel (Kv4.3), acetylcholine-dependent potassium channel (Kir3.4) and ATP-dependent potassium channel (Kir6.2) were reduced in patients with persistent AF (-35%, -47% and -36%, respectively, p < 0.05), whereas only Kv4.3 mRNA level was reduced in patients with paroxysmal AF (-29%, p = 0.03). No changes were found for Kv1.5 and HERG mRNA levels in either group. Protein levels of Kv4.3, Kv1.5 and Kir3.1 were reduced both in patients with persistent AF (-39%, -84% and -47%, respectively, p < 0.05) and in those with paroxysmal AF (-57%, -64%, and -40%, respectively, p < 0.05). CONCLUSIONS: Persistent AF is accompanied by reductions in mRNA and protein levels of several potassium channels. In patients with paroxysmal AF these reductions were observed predominantly at the protein level and not at the mRNA level, suggesting a post-transcriptional regulation.

Aged↗
PubMed2001

Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation.

BACKGROUND: Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF. METHODS AND RESULTS: mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation. CONCLUSIONS: AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

Atrial Fibrillation↗
PubMed2001

Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity.

OBJECTIVES: To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. DESIGN: Cross-sectional cohort study. SETTING: Inhabitants of the city of Groningen, the Netherlands. SUBJECTS: All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. MAIN OUTCOME MEASURES: Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. RESULTS: Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. CONCLUSIONS: Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.

Adult↗
PubMed2001

Endothelin system in human persistent and paroxysmal atrial fibrillation.

INTRODUCTION: Activation of the endothelin system is an important compensatory mechanism that is activated during left ventricular dysfunction. Whether this system plays a role at the atrial level during atrial fibrillation (AF) has not been examined in detail. The purpose of this study was to investigate mRNA and protein expression levels of the endothelin system in AF patients with and without concomitant underlying valve disease. METHODS AND RESULTS: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 controls in sinus rhythm. The mRNA amounts of pro-endothelin-1 (pro-ET-1), endothelin receptor A (ET-A), and endothelin receptor B (ET-B) were studied by semiquantitative polymerase chain reaction. Protein amounts of the receptors were investigated by slot-blot analysis. mRNA amounts of pro-ET-1 were increased (+40%; P = 0.002) only in AF patients with underlying valve disease. ET-A and ET-B receptor protein amounts were significantly reduced in patients with paroxysmal AF (-39% and -47%, respectively) and persistent AF with underlying valve disease (-28% and -30%, respectively) and in persistent AF without valve disease (-20% and -40%, respectively). ET-A mRNA expression was unaltered in paroxysmal and persistent AF, whereas ET-B mRNA was reduced by 30% in persistent AF with (P < 0.001) or without (P = 0.04) valve disease, but unchanged in paroxysmal AF. CONCLUSION: Substantial changes in gene expression of the endothelin system were observed in human atria during AF, especially in the presence of underlying valve disease. Alterations in endothelin expression associated with AF could play a role in the pathophysiology of AF and the progression of underlying heart disease.

Aged↗
PubMed1999

Gene expression of the natriuretic peptide system in atrial tissue of patients with paroxysmal and persistent atrial fibrillation.

INTRODUCTION: Circulating cardiac natriuretic peptides play an important role in maintaining volume homeostasis, especially during conditions affecting hemodynamics. During atrial fibrillation (AF), levels of plasma atrial natriuretic peptide (ANP) becomes elevated. The aim of this study was to gather information about gene expression of the natriuretic peptide system on the atrial level in patients with AF. METHODS AND RESULTS: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 case matched controls in sinus rhythm for mRNA expression of pro- atrial natriuretic peptide (pro-ANP), pro-brain natriuretic peptide (pro-BNP), and their natriuretic peptide receptor type-A (NPR-A). We investigated patients without (n = 36) and with (n = 36) valvular disease. Persistent AF was associated with higher mRNA expression of pro-BNP (+66%, P = 0.04, in patients without valvular disease, and +69%, P < 0.01, in patients with valvular disease) and lower mRNA expression of NPR-A (-58%, P = 0.02, in patients without valvular disease, and -62 %, P < 0.01, in patients with valvular disease). The mRNA content of pro-ANP was only increased in patients with valvular disease (+12%, P = 0.03). No changes were observed in patients with paroxysmal AF. CONCLUSION: This study demonstrates that persistent, but not paroxysmal, AF induces alterations in gene expression of pro-BNP and NPR-A on the atrial level. Although AF generally is associated with an increase of plasma ANP level, a change in mRNA content of pro-ANP is only observed in the presence of concomitant valvular disease and is of minor magnitude.

Adult↗
PubMed1999

Alterations in gene expression of proteins involved in the calcium handling in patients with atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) leads to a loss of atrial contraction within hours to days. During persistence of AF, cellular dedifferentiation and hypertrophy occur, eventually resulting in degenerative changes and cell death. Abnormalities in the calcium handling in response to tachycardia-induced intracellular calcium overload play a pivotal role in these processes. METHODS AND RESULTS: The purpose was to investigate the mRNA expression of proteins and ion channels influencing the calcium handling in patients with persistent AF. Right atrial appendages were obtained from 18 matched controls in sinus rhythm (group 1) and 18 patients with persistent AF undergoing elective cardiac surgery. Previous duration of AF was < or = 6 months in 9 (group 2) and > 6 months in 9 patients (group 3). In a single semiquantitative polymerase chain reaction, the mRNA of interest and of glyceraldehyde-3-phosphate dehydrogenase, were coamplified and separated by gel electrophoresis. L-type calcium channel alpha1 subunit mRNA content was inversely related to the duration of AF: -26% in group 2 compared to group 1 (P = 0.2), and -49% in group 3 compared to group 1 (P = 0.01). Inhibitory guanine nucleotide binding protein ialpha2 mRNA content was reduced in group 3 compared to group 1 (-30%, P = 0.01). Sarcoplasmic reticulum calcium ATPase, phospholamban and sodium-calcium exchanger mRNA contents were not affected by AF. CONCLUSIONS: AF-induced alterations in mRNA contents of proteins and ion channels involved in the calcium handling seem to occur in relation to the previous duration of AF. In the present patient population, these changes were significant only if AF lasted > 6 months.

Aged↗
PubMed1994

Left ventricular dilatation and high-grade ventricular arrhythmias in the first year after myocardial infarction. CATS Investigators. Captopril and Thrombolysis Study.

Progressive left ventricular dilatation is an important determinant of prognosis after myocardial infarction. The association of this process with the occurrence of ventricular arrhythmias is less well established. Of 153 patients with a first anterior myocardial infarction treated with thrombolytic therapy, 34 (22%) had high-grade ventricular arrhythmias (Lown 4A and B) during Holter monitoring after 1 year. Patients with high-grade ventricular arrhythmias had a larger end-systolic volume (38 +/- 12 vs 25 +/- 11 mL/m2; P < .001) at hospital discharge and more left ventricular dilatation (10 +/- 18 vs 1 +/- 9 mL/m2; P = .011) during the follow-up period. Increased end-systolic volume at discharge and subsequent dilatation proved to be independent predictors of high-grade ventricular arrhythmias. Six patients died suddenly during the first 12 months after myocardial infarction. Four of these patients had an enlarged end-systolic volume (> 22 mL/m2) at discharge, and the three patients who died suddenly after 3 months showed a significant increase in end-systolic volume from discharge to 3 months compared to survivors (16 +/- 6 vs 2 +/- 9; P = .008). Left ventricular remodeling after myocardial infarction is an independent predictor of the occurrence of ventricular arrhythmias late after myocardial infarction.

Aged↗
PubMed1993

Cardioprotection by angiotensin-converting enzyme (ACE) inhibitors.

OBJECTIVE: To focus on the cardioprotective role of angiotensin-converting enzyme (ACE) inhibitors in ischemic heart disease and to highlight some of the, as yet, unanswered questions about the relative merits of ACE inhibitors as cardioprotective drugs. DATA SOURCE: This review incorporates the data on this subject published in the available English literature up to June 1990. DATA SELECTION: The source material was analyzed and computed chronologically into two groups: experimental studies and clinical trials. DATA EXTRACTION: ACE inhibitors have gained access to the free world market for a variety of reasons. Their superiority in the management of hypertension and congestive heart failure is being recognized. Furthermore, recent experimental and limited clinical trials strongly indicate a role for ACE inhibitors in limiting myocardial ischemia-reperfusion-induced injury. Although the sulphydryl group (SH)-containing ACE inhibitor captopril has been extensively used for most studies, the cardioprotective role of non-SH-containing ACE inhibitors, particularly ramipril and enalapril, recently has been identified. ACE inhibitors reportedly limit infarct size, prevent ventricular remodelling and, more importantly, stabilize the electrical activity of the reperfused heart and prevent the occurrence of reperfusion arrhythmias. Preliminary clinical trials indicate an antianginal role for ACE inhibitors. ACE inhibition has also been reported to improve left ventricular performance in patients with long standing infarcts and ischemic failure. Although pharmacological effects of ACE inhibitors are well known, the mechanism of cardioprotection at the molecular and cellular levels is elusive. The role of ACE inhibitors in myocardial stunning and their free radical scavenging effects are still speculative. Furthermore, the effects of ACE inhibition during global myocardial ischemia-reperfusion are virtually unknown. CONCLUSIONS: The available data strongly indicates a role for ACE inhibitors in limiting myocardial ischemia-reperfusion-induced injury. However, more controlled studies, particularly multicentre clinical trials, are indicated to establish a therapeutic rationale for ACE inhibition in the management of ischemic heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Triggered activity as arrhythmogenic mechanism after myocardial infarction: clinical and electrophysiologic study of one case.

In a woman with an old infarction and sustained ventricular tachycardia, tachycardias were only inducible after short-long RR sequences. After isoprenaline, tachycardias became incessant and all were preceded by short-long RR sequences. This strongly suggests that triggered activity plays a role in initiation of ventricular tachycardias in postinfarction patients.

Aged↗
PubMed1991

Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter.

The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events.

Actuarial Analysis↗
PubMed1991

Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter.

The present study was undertaken to reassess prospectively the immediate and long-term results of direct-current electrical cardioversion in chronic atrial fibrillation or atrial flutter, and to determine factors predicting clinical outcome of the arrhythmia after direct-current cardioversion. Two-hundred forty-six patients underwent direct-current electrical cardioversion and were followed during a mean of 260 days. Multivariate analysis was used to identify factors predicting short- and long-term arrhythmia outcome. Cardioversion was achieved in 70% of patients with atrial fibrillation and in 96% of patients with atrial flutter. Stepwise logistic regression analysis revealed that arrhythmia duration (p less than 0.001), type of arrhythmia (fibrillation vs flutter, p less than 0.02) and age (p less than 0.05) independently influenced conversion rate. On an actuarial basis, 42 and 36% of patients remained in sinus rhythm during 1 and 2 years, respectively. Multivariate regression analysis revealed that the type of arrhythmia (p = 0.0008), low precardioversion functional class (p = 0.002) and the presence of nonrheumatic mitral valve disease (p = 0.03) independently increased the length of the arrhythmia-free episode. Rheumatic heart disease shortened this period (p = 0.03). In conclusion, patients having a high probability of conversion together with a prolonged post-shock arrhythmia-free episode can be identified. This may improve the cost-benefit ratio of cardioversion.

Adult↗
PubMed1991

Incidence and clinical significance of ST segment elevation after electrical cardioversion of atrial fibrillation and atrial flutter.

To study the incidence and clinical significance of postshock ST segment elevations, we recorded 12-lead ECGs immediately after transthoracic direct-current electrical cardioversion in 146 patients with atrial fibrillation or flutter. Among 23 patients (19%), acute ST segment elevations amounted to 1.4 +/- 0.8 mV (mean +/- SD) and occurred after 243 +/- 114 joules (cumulative dose) in the precordial leads only in 14, concomitantly in precordial and inferior leads in two, and in the precordial and anterolateral leads in seven. They normalized within 1.5 +/- 0.8 minutes. Occurrence of ST segment elevation was related to previous pericardiotomy (p less than 0.00001) and age (p = 0.01). Estimation of myocardial enzyme release did not show evidence of myocardial damage. Patients with ST segment elevations had a lower conversion rate (48% versus 76%, p = 0.005). Long-term maintenance of sinus rhythm was also diminished (35% versus 59%, p = 0.03). Results of this study show that postcardioversion ST segment elevation occurs predominantly in postpericardiotomy patients and may be associated with an unfavorable arrhythmia prognosis.

Age Factors↗
PubMed1991

The oral dopamine agonist, ibopamine, in normal man: effects on rhythm, heart rate, blood pressure and catecholamines.

To evaluate the effects of the oral aselective dopamine congener ibopamine, heart rate, blood pressure, cardiac rhythm, electrocardiographic (ECG) parameters and plasma catecholamines were studied in ten healthy subjects on three occasions: without medication, after 100 mg oral ibopamine and after combined treatment of ibopamine and the dopamine antagonist metoclopramide. Ibopamine was well tolerated by all subjects. No significant changes in heart rate or blood pressure were seen during either ibopamine alone or during concomitant metoclopramide administration. In addition, there were no differences in PR-, QRS- and QTc- intervals on the ECG and plasma norepinephrine, epinephrine and dopamine levels were unchanged. None of the ten volunteers showed proarrhythmia from ibopamine. However, in one subject, episodes of accelerated idioventricular rhythm were observed after ibopamine, which were asymptomatic and did not exceed a rate of 51 beats/minute. During concomitant metoclopramide infusion, ibopamine did not induce accelerated idioventricular rhythm. In conclusion, in healthy subjects ibopamine appears to be a safe drug and causes neither proarrhythmia, nor changes in heart rate, blood pressure, ECG-parameters, or plasma catecholamines.

Administration, Oral↗
PubMed1989

Efficacy and safety of flecainide acetate in the maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation or atrial flutter.

The efficacy and safety of flecainide were studied in the maintenance of sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. Eighty-one patients were randomized to flecainide treatment or no treatment. Baseline characteristics of both groups were comparable. Compared to previous studies, patients could be classified as difficult-to-treat patients. Multiple regression analysis showed New York Heart Association class I for exercise tolerance (p = 0.0004) and flecainide treatment (p = 0.01) to be the main factors increasing the arrhythmia-free episode. However, Mantel-Cox lifetable analysis did not reveal significant differences between arrhythmia-free survival curves of both treatment groups. In the flecainide-treated group, 9% of patients experienced side effects, mostly related to negative dromotropic effects. The incidence of ventricular proarrhythmia in this group of patients was low. Thus, flecainide may be effective in postponing arrhythmia recurrence, even in difficult-to-treat patients. Caution should be excercised in treating patients with underlying conduction disturbances, sick sinus syndrome or characteristics favoring development of ventricular proarrhythmia.

Adolescent↗