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A A M Wilde

Publications and source records attributed to A A M Wilde.

At least 19 recordsLinked to original sources
PubMed2006

[Medication for ADHD and the risk of cardiovascular mortality].

Recently, the FDA recommended a black-box warning describing the increased risk of cardiovascular events associated with the use of stimulant drugs (amphetamines; in the Netherlands: dexamphetamine, methylphenidate) in the treatment of attention deficit hyperactivity disorder (ADHD). The recommendation was based largely on the increased use of these drugs in children and adults in the USA, voluntary reporting of adverse events, and the pharmacological analogy with other sympathomimetic amines, such as ephedrine, pseudoephedrine and phenylpropanolamine, for which similarwarnings have been given previously. The Adverse Event Reporting System documented 25 cases of sudden death based on WHO criteria with the use of amphetamines and methylphenidate; most of the cases were children aged less than 18 years. Sudden death in children is most often caused by fatal arrhythmias due to congenital heart diseases, such as long QT syndrome and hypertrophic cardiomyopathy. An increase in heart rate can potentially provoke life-threatening arrhythmias when the QT interval does not compensate for the increase. In adults, increased blood pressure and heart rate are well-documented risk factors for cardiovascular events. The use of methylphenidate is increasing in the Netherlands, indicating that greater caution is warranted when prescribing these drugs.

Amphetamine↗
PubMed2005

Can parents adjust to the idea that their child is at risk for a sudden death?: Psychological impact of risk for long QT syndrome.

Can a parent adjust to the idea that its child is at risk for a sudden death? This question is raised by a diagnostic procedure in which children were tested for an inherited Long QT Syndrome (LQTS). This potentially life-threatening but treatable cardiac arrhythmia syndrome may cause sudden death, especially in children and young adults. The long-term psychological effects are described for parents whose children were tested for inherited LQTS. The adverse short-term impact of such testing has been described previously. The goal of this investigation is to determine whether this distress endures. Thirty-six parents completed measures of psychological distress. With the twenty-four parents of carrier children, a semi-structured interview was held 18 months after DNA disclosure. Parents of carrier children reported more distress than parents of non-carrier children. Parents of carrier children remained vulnerable to high levels of distress; up to one-third of these parents showed clinically relevant high levels of distress. High levels of distress were reported by parents of carrier children who (1) were highly distressed at previous assessments, (2) were familiar with the disease for a longer time, (3) had experienced a sudden death in the family, (4) were lesser educated, and who (5) were unsatisfied with the given information. Parents were particularly concerned about possible hazardous behavior during puberty. We conclude that the continuous threat of developing LQTS symptoms despite prophylactic treatment affected the psychological well-being of the parents for a long time. In light of the tempetuous developments in the areas of cardiac genetics, periodical information on new insight and developments may act as a buffer for the parents' (growing) concerns about their child's inherited disorder.

Adolescent↗
PubMed2005

[Sudden death at young age and the importance of molecular-pathologic investigation].

The autopsy of a 16-year-old boy who had died suddenly revealed hypertrophic cardiomyopathy (HCM). Molecular genetic investigation revealed mutations in the MYBPC3 gene. His surviving family members could then be examined and reassured that they did not carry the mutation. An 18-year-old boy who died suddenly turned out to have known HCM. No further investigations were done and no tissue was saved. Genetic investigation of his immediate family was impossible due to the lack of a known mutation in the family. Periodic examination in clinically unaffected family members was therefore advised. Sudden cardiac death at young age is not infrequently the first symptom of an inherited cardiac disease. Because these diseases usually inherit as an autosomal dominant trait, first-degree family members have a 50% chance of carrying the same genetic defect. Besides clinical cardiologic examination of the remaining family members, post-mortem molecular genetic investigation can be of value in reaching a diagnosis and in determining the subsequent therapeutic options for immediate relatives.

Adolescent↗
PubMed2005

Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties.

AIM: Brugada syndrome is an inherited cardiac disease with an increased risk of sudden cardiac death. Thus far Brugada syndrome has been linked only to mutations in SCN5A, the gene encoding the alpha-subunit of cardiac Na+ channel. In this study, a novel SCN5A gene mutation (D1714G) is reported, which has been found in a 57-year-old male patient. Since the mutation is located in a segment of the ion-conducting pore of the cardiac Na+ channel, which putatively determines ion selectivity, it may affect ion selectivity properties. METHODS: HEK-293 cells were transfected with wild-type (WT) or D1714G alpha-subunit and beta-subunit cDNA. Whole-cell configuration of the patch-clamp technique was used to study biophysical properties at room temperature (21 degrees C) and physiological temperature (36 degrees C). This study represents the first measurements of human Na+ channel kinetics at 36 degrees C. Ion selectivity, current density, and gating properties of WT and D1714G channel were studied. RESULTS: D1714G channel yielded nearly 80% reduction of Na+ current density at 21 and 36 degrees C. At both temperatures, no significant changes were observed in V(1/2) values and slope factors for voltage-dependent activation and inactivation. At 36 degrees C, but not at 21 degrees C, D1714G channel exhibited more slow inactivation compared with WT channel. Ion selectivity properties were not affected by the mutation at both temperatures, as assessed by either current or permeability ratio. CONCLUSION: This study shows no changes in ion selectivity properties of D1714G channel. However, the profoundly decreased current density associated with the D1714G mutation may explain the Brugada syndrome phenotype in our patient.

Animals↗
PubMed2005

Preferences of cardiologists and clinical geneticists for the future organization of genetic care in hypertrophic cardiomyopathy: a survey.

In view of the increasing demands for genetic counselling and DNA diagnostics in cardiogenetics, the roles of cardiologists and clinical geneticists in the delivery of care need to be redefined. We investigated the preferences of both groups of professionals with regard to the future allocation of six cardiogenetic responsibilities in counselling and testing, using hypertrophic cardiomyopathy (HCM) as a prevalent model disease. In this cross-sectional survey, the participants were Dutch cardiologists (n = 643) and clinical geneticists (n = 60), all members of professional societies. Response rates were 33 and 82%, respectively. In both groups, the majority preferred to perform most of the tasks described above in collaboration. Informing HCM patients about the genetics of HCM and requesting DNA testing in symptomatic patients was viewed by 43 and 35% of cardiologists, respectively, as their sole responsibility, however, and 39 and 59% of clinical geneticists did not object to these views. Both groups felt that the task of discussing the consequences of HCM for offspring and that of discussing the results of DNA diagnostics should be shared or performed by clinical geneticists. Both groups considered co-ordination of family screening the sole responsibility of clinical geneticists. Opinions on who should request DNA diagnostics in asymptomatic relatives were divided: 86% of clinical geneticists considered it their exclusive responsibility, 10% of cardiologists believed that this task could be performed individually by either group and 30% preferred to collaborate. Most professionals said that they would appreciate education programmes and clinical guidelines. Both cardiologists and clinical geneticists prefer to share rather than divide most cardiogenetic responsibilities in caring for HCM patients. Consequently, capacity problems in both groups are to be expected. To safeguard current professional standards in genetic counselling and testing, deployment of non-medical personnel might be essential.

Attitude of Health Personnel↗
PubMed2005

Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients.

BACKGROUND: The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands. METHODS AND RESULTS: We identified 13 missense mutations in the cardiac ryanodine receptor (RYR2) in 12 probands with CPVT. Twelve were new, of which two are de novo mutations. A further 11 patients were silent gene carriers, suggesting that some mutations are associated with low penetrance. A marked resting sinus bradycardia off drugs was observed in all carriers. On beta blocker treatment, 98% of the RYR2 mutation carriers remained symptom free with a median follow up of 2 (range: 2-37) years. CONCLUSION: CPVT patients with RYR2 mutation have bradycardia regardless of the site of the mutation, which could direct molecular diagnosis in (young) patients without structural heart disease presenting with syncopal events and a slow heart rate but with normal QTc at resting ECG. Treatment with beta blockers has been very effective in our CPVT patients during initial or short term follow up. Given the risk of sudden death and the efficacy of beta blocker therapy, the identification of large numbers of RYR2 mutations thus calls for genetic screening, early diagnosis, and subsequent preventive strategies.

Adolescent↗
PubMed2005

High distress in parents whose children undergo predictive testing for long QT syndrome.

OBJECTIVES: To assess the psychological effect of predictive testing in parents of children at risk for long QT syndrome (LQTS) in a prospective study. METHODS: After their child was clinically screened by electrocardiography and blood was taken for DNA analysis, and shortly after delivery of the DNA test result, 36 parents completed measures of psychological distress. RESULTS: 24 parents were informed that at least one of their children is a mutation carrier. Up to 50% of the parents of carrier children showed clinically relevant high levels of distress. Parents who were familiar with the disease for a longer time, who had more experiences with the disease in their family and who received positive test results for all their children were most distressed. CONCLUSIONS: Predictive ECG testing together with DNA testing has a profound impact on parents whose minors undergo predictive testing for LQTS.

Adolescent↗
PubMed2004

A patient with recurrent syncope and ST-elevation on the electrocardiogram.

A 56-year old woman had over 100 episodes of syncope since the age of 8. Because the patient's description of the episodes suggested vasovagal syncope she was studied by a head up tilt test (HUT). Seconds after the uncomplicated HUT the patient experienced a typical syncope with bradycardia, marked ST-elevation and chest pain. After treatment with nifedipine she has had one syncopal spell in a follow up period of 31 months. We conclude that the syncopal events in this patient were caused by a combination of vasovagal syncope and coronary spasm.

Calcium Channel Blockers↗
PubMed2004

Family and population strategies for screening and counselling of inherited cardiac arrhythmias.

Family screening in inherited cardiac arrhythmias has been performed in The Netherlands since 1996, when diagnostic DNA testing in long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) became technically possible. In multidisciplinary outpatient academic clinics, an adjusted protocol for genetic counselling, originally derived from predictive testing in Huntington's disease, is being used. 1110 individuals, including 842 relatives of index patients, were informed about their risks, and most were tested molecularly and/or clinically for carriership of the disease present in their family. Of 345 relatives who were referred for cardiologic follow-up, 189 are being treated, because of an increased risk of life-threatening arrhythmias. Evaluation of the psychological and social consequences of family screening for inherited arrhythmias can be performed by using the adapted criteria of Wilson and Jüngner, i.e., from a point of view of public health. Preliminary results of psychological research show that parents of children at risk for LQTS show high levels of distress. Many other aspects have to be evaluated yet, making final conclusions about the feasibility of family screening difficult, particularly in HCM. Clinical guidelines are urgently needed. Population screening by molecular testing, for instance in athletic preparticipation screening, will become possible in the future and has its own prerequisites for success.

Arrhythmias, Cardiac↗
PubMed2003

[Initial diagnostic strategy in the case of transient losses of consciousness: the importance of the medical history].

It is estimated that almost half of the people experience a transient loss of consciousness at some time during their life. In young patients (< 35 years) the cause is mostly a reflex syncope. In older patients the common causes are orthostatic and postprandial hypotension, sinus caroticus syndrome, cardiac arrhythmias and valvular disorders. The medical history can identify a probable cause of the transient loss of consciousness in almost all young patients (< 35 years) and in the majority of older patients. A physical examination and an ECG should be performed in all patients who have experienced a transient loss of consciousness, other than those with classical vasovagal syncope, in order to exclude orthostatic hypotension and dangerous cardiac causes.

Adult↗
PubMed2003

Genetic knowledge and counselling skills of Dutch cardiologists: sufficient for the genomics era?

AIMS: Genetic scientific knowledge is growing rapidly but how this affects clinical practice is unclear. We investigated the levels of knowledge, practical skills and clinical genetic practices of Dutch cardiologists. METHODS AND RESULTS: A survey was designed to assess cardiologists' experience with genetic aspects of hypertrophic cardiomyopathy, self-reported genetic knowledge, and genetic skills in general and aimed at this disease. In addition, cardiologists' opinions on five possible measures for improvement were obtained. STUDY POPULATION: all Dutch cardiologists (n=643). Median number of patients suffering from hypertrophic cardiomyopathy per cardiologist is five. Forty-one percent of respondents do not give information about genetics to all their patients. Cardiologists rarely initiate DNA tests for hypertrophic cardiomyopathy. Only 38% refer patients to clinical geneticists. Self-reported knowledge levels are low (average score 3.3-5.1, 0-10 scale). Cardiologists with an established working relationship with a clinical geneticist report significantly higher levels of knowledge. Clinical guidelines, education and improved collaboration with clinical geneticists are preferred. CONCLUSION: Dutch cardiologists' genetic knowledge and clinical genetic practice levels are insufficient. As a result, clinical genetic care for patients with hypertrophic cardiomyopathy is poor. Improvements proposed include advancement of knowledge (education, professional guidelines) and structural measures (working relationships, multidisciplinary outpatient clinics). Collaboration of cardiologists and clinical geneticists is urgently needed to optimise cardiogenetic patient care.

Adult↗
PubMed2002

[Hypertrophic cardiomyopathy: a genetically-carried heart disease].

Hypertrophic cardiomyopathy (HCM) is a cardiac muscle disease with characteristic (mostly asymmetrically distributed) hypertrophy of a non-dilated left ventricle in the absence of another cardiac or systemic disease that can cause left ventricle hypertrophy. The prevalence of HCM in the general population is estimated to be 1 in 500 persons. It is an inheritable disease of the heart with a heterogeneous expression and a great diversity of morphological, functional and clinical features. The genes involved code for components of a large protein complex ('the sarcomere'), which ensures the contraction of the cardiac muscle. Electrocardiography, echocardiography and cardiac MRI play a role in the diagnosis. Medicinal treatment can improve the diastolic filling and the ventricle function. In addition to this there are surgical and non-surgical possibilities for myocardial reduction. For patients with life-threatening arrhythmias and for the primary prevention of sudden death for high-risk patients, an internally implantable cardioverter-defibrillator is indicated. The early detection of patients with a predisposition for HCM is only possible by means of genotyping.

Cardiomyopathy, Hypertrophic, Familial↗
PubMed2002

Brugada syndrome.

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Bundle-Branch Block↗