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P A van der Zwaag,
I A W van Rijsingen,
R de Ruiter,
E A Nannenberg,
J A Groeneweg,
J G Post,
R N W Hauer,
I C van Gelder, M P van den Berg,
P van der Harst,
A A M Wilde,
J P van Tintelen
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Recently, we showed that the c.40_42delAGA (p.Arg14del) mutation in the phospholamban (PLN) gene can be identified in 10-15 % of Dutch patients with dilated cardiomyopathy or arrhythmogenic cardiomyopathy. The arrhythmogenic burden of the p.Arg14del mutation was illustrated by the high rate of appropriate ICD discharges and a positive family history for sudden cardiac death. METHODS: Our goal was to evaluate the geographical distribution and the origin of this specific mutation in the Netherlands and to get an estimation of the prevalence in a Dutch population cohort. Therefore, we investigated the postal codes of the places of residence of PLN p.Arg14del mutation carriers and places of birth of their ancestors. In addition, a large population-based cohort (PREVEND) was screened for the presence of this mutation. RESULTS: By April 2012, we had identified 101 probands carrying the PLN p.Arg14del mutation. A total of 358 family members were also found to carry this mutation, resulting in a total of 459 mutation carriers. The majority of mutation carriers live in the northern part of the Netherlands and analysing their grandparents' places of birth indicated that the mutation likely originated in the eastern part of the province of Friesland. In the PREVEND cohort we identified six heterozygous PLN p.Arg14del mutation carriers out of 8,267 subjects (0.07 %). CONCLUSION: The p.Arg14del mutation in the PLN gene is the most frequently identified mutation in Dutch cardiomyopathy patients. The mutation that arose 575-825 years ago is likely to have originated from the eastern part of the province of Friesland and is highly prevalent in the general population in the northern part of the Netherlands.
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2013; · 1.44 Impact Factor
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Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 03/2013; · 1.44 Impact Factor
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P.A. van der Zwaag,
M.G.P.J. Cox,
C. van der Werf,
A.C.P. Wiesfeld,
J.D.H. Jongbloed,
D. Dooijes,
H. Bikker,
R. Jongbloed,
A.J.H. Suurmeijer, M.P. van den Berg,
R.M.W. Hofstra,
R.N.W. Hauer,
A.A.M. Wilde,
J.P. van Tintelen
[show abstract]
[hide abstract]
ABSTRACT: Background. Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance
and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p.Arg79X mutation in PKP2 has been identified in Europe and North America
and has been functionally characterised. We evaluated the prevalence of the p.Arg79X mutation in PKP2 in the Dutch population.
Methods. Twelve index patients and 41 family members were evaluated in three university hospitals in the Netherlands. The diagnosis
of ARVC/D was established according to the recently revised Task Force Criteria. Segregation of the p.Arg79X mutation was
studied and haplotypes were reconstructed to determine whether the p.Arg79X mutation was a recurrent or a founder mutation.
Results. The p.Arg79X mutation in PKP2 was identified in 12 index patients. Haplotype analysis revealed a shared haplotype among
Dutch p.Arg79X mutation carriers, indicating a common founder. Six index patients (50%) had a first- or second-degree relative
who had died of sudden cardiac death below 40 years of age. At age 60, only 60% of the mutation carriers had experienced any
symptoms. There was no significant difference in symptom-free survival and event-free survival between men and women.
Conclusion. We have identified the largest series of patients with the same desmosome gene mutation in ARVC/D reported to date. This
p.Arg79X mutation in PKP2 is a founder mutation in the Dutch population. The phenotypes of PKP2 p.Arg79X mutation carriers
illustrate the clinical variability and reduced penetrance often seen in ARVC/D. (Neth Heart J 2010;18:583–91.)
KeywordsCardiomyopathy–ARVC/D–Genetics–PKP2–Founder Mutation
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2012; 18(12):583-591. · 1.44 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Background/Methods. Marfan syndrome (MFS) is a heritable connective tissue disorder usually caused by a mutation in the fibrillin 1 (FBN1) gene. Typical characteristics of MFS that have been described include dolichostenomelia, ectopia lentis and aortic root
dilatation. However, there is great clinical variability in the expression of the syndrome’s manifestations, both between
and within families. Here we discuss the clinical variability of MFS by describing a large fourgeneration Dutch family with
MFS.
Results. Nineteen individuals of one family with a single missense FBN1 mutation (c.7916A>G) were identified. The same mutation was found in one unrelated person. Clinical variability was extensive
and not all mutation carriers fulfilled the diagnostic criteria for MFS. Some patients only expressed mild skeletal abnormalities,
whereas aortic root dilation was present in eight patients, an acute type A aortic dissection was recorded in two other patients,
and a mitral valve prolapse was present in eight patients. In some patients cardiac features were not present on initial screening,
but did however develop over time.
Conclusion. MFS is a clinically highly variable syndrome, which means a meticulous evaluation of suspected cases is crucial. Mutation
carriers should be re-evaluated regularly as cardiovascular symptoms may develop over time. (Neth Heart J 2010;18:85–9.)
Marfan Syndrome/genetics-Microfilament Proteins-Mutation-Missense-Netherlands
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2012; 18(2):85-89. · 1.44 Impact Factor
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E. Otten,
R. H. Lekanne dit Deprez,
M. M. Weiss,
M. van Slegtenhorst,
M. Joosten,
J. J. van der Smagt,
N. de Jonge,
W. S. Kerstjens-Frederikse,
M. T. R. Roofthooft,
A. H. M. M. Balk, M. P. van den Berg,
J. S. Ruiter,
J. P. van Tintelen
[show abstract]
[hide abstract]
ABSTRACT: Background. About 30% of dilated cardiomyopathy (DCM) cases are familial. Mutations are mostly found in the genes encoding lamin A/C,
beta-myosin heavy chain and the sarcomeric protein cardiac troponin-T (TNNT2). Mutations in TNNT2 are reported in approximately 3% of DCM patients. The overall phenotype caused by TNNT2 mutations is thought to be a fully penetrant, severe disease. This also seems to be true for a recurrent deletion in the
TNNT2 gene; p.K217del (also known as p.K210del).
Methods. We compared the phenotype of all Dutch patients identified as carrying the TNNT2 p.K217del mutation with those described in the literature. All index patients underwent cardiological evaluation. Family
screening was done in all described families.
Results. Six DCM patients carrying the TNNT2 p.K217del mutation were identified from four Dutch families. Mean age of disease manifestation was 33 years. Heart transplantation
was required in three of them at ages 12, 18 and 19 years. These outcomes are comparable with those described in the literature.
Conclusion. Carriers of the TNNT2 p.K217del mutation in our Dutch families, as well as in families described in the literature before, generally show a severe,
early-onset form of DCM. (Neth Heart J 2010;18:478-85.)
Cardiomyopathy-Dilated-Genetics-Troponin T
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2012; 18(10):478-485. · 1.44 Impact Factor
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P. G. Postema, M. P. Van den Berg,
J. P. Van Tintelen,
F. Van den Heuvel,
M. Grundeken,
N. Hofman,
W. P. Van der Roest,
E. A. Nannenberg,
I. P. C. Krapels,
C. R. Bezzina,
A. A. M. Wilde
[show abstract]
[hide abstract]
ABSTRACT: In this part of a series on founder mutations in the Netherlands, we review a Dutch family carrying the SCN5a 1795insD mutation. We describe the advances in our understanding of the premature sudden cardiac deaths that have accompanied
this family in the past centuries. The mutation carriers show a unique overlap of long-QT syndrome (type 3), Brugada syndrome
and progressive cardiac conduction defects attributed to a single mutation in the cardiac sodium channel gene SCN5a. It is at present one of the largest and best-described families worldwide and we have learned immensely from the mouse strains
with the murine homologue of the SCN5a 1795insD mutation (SCN5a 1798insD). From the studies currently performed we are about to obtain new insights into the phenotypic variability in this
monogenic arrhythmia syndrome, and this might also be relevant for other arrhythmia syndromes and the general population.
(Neth Heart J 2009;17:422–8.)
long-QT syndrome-Brugada syndrome-conduction disease-cardiac sodium channel disease-sudden cardiac death
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2012; 17(11):422-428. · 1.44 Impact Factor
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K Y van Spaendonck-Zwarts,
A J van der Kooi, M P van den Berg,
E F Ippel,
L G Boven,
W-C Yee,
A van den Wijngaard,
E Brusse,
J E Hoogendijk,
P A Doevendans,
M de Visser,
J D H Jongbloed,
J P van Tintelen
[show abstract]
[hide abstract]
ABSTRACT: Desmin-related myopathy (DRM) is an autosomally inherited skeletal and cardiac myopathy, mainly caused by dominant mutations in the desmin gene (DES). We describe new families carrying the p.S13F or p.N342D DES mutations, the cardiac phenotype of all carriers, and the founder effects.
We collected the clinical details of all carriers of p.S13F or p.N342D. The founder effects were studied using genealogy and haplotype analysis.
We identified three new index patients carrying the p.S13F mutation and two new families carrying the p.N342D mutation. In total, we summarised the clinical details of 39 p.S13F carriers (eight index patients) and of 21 p.N342D carriers (three index patients). The cardiac phenotype of p.S13F carriers is fully penetrant and severe, characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement. Although muscle weakness is a prominent and presenting symptom in p.N342D carriers, their cardiac phenotype is similar to that of p.S13F carriers. The founder effects of p.S13F and p.N342D were demonstrated by genealogy and haplotype analysis.
DRM may occur as an apparently isolated cardiological disorder. The cardiac phenotypes of the DES founder mutations p.S13F and p.N342D are characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement.
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 01/2012; 20(5):219-28. · 1.44 Impact Factor
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R Altena,
Y M Hummel,
J Nuver,
A J Smit,
J D Lefrandt,
R A de Boer,
A A Voors, M P van den Berg,
E G E de Vries,
H M Boezen,
J A Gietema
[show abstract]
[hide abstract]
ABSTRACT: Cross-sectional studies showed that treatment with cisplatin chemotherapy for testicular cancer is associated with an increased incidence of cardiac dysfunction. We investigated longitudinal progression of and contributing factors to cardiac dysfunction in testicular cancer survivors.
Cardiac assessments were carried out before 10 months (range 7-15 months) and 6.9 years (range 4.9-9.7 years) after start of cisplatin-based chemotherapy, consisting of echocardiography [systolic function (left ventricular ejection fraction, LVEF), diastolic function (myocardial tissue velocities; tissue velocity imaging of early diastole, TVI Et)] and plasma biomarkers (N-Terminal pro brain natriuretic peptide, NT-proBNP; galectin-3).
In 37 patients [median age 34 years (range 24-51 years)], the incidence of abnormal TVI Et increased from 0% at baseline and 4.5% at 10 months (in 27 patients) to 16.7% at 6.9 years post-chemotherapy (P = 0.03). One patient developed LVEF <50%; no other systolic abnormalities occurred. Hypertension, obesity and age were associated with larger decreases in TVI Et. Changes in NT-proBNP and galectin-3 were not related to echocardiographic abnormalities.
In this longitudinal cohort study, we observed a gradual decline in diastolic parameters after cisplatin-based chemotherapy for testicular cancer, whereas the rate of systolic dysfunction remains low. The association of larger declines in diastolic parameters with hypertension and obesity stresses the need to monitor and treat cardiovascular risk factors.
Annals of Oncology 08/2011; 22(10):2286-93. · 6.43 Impact Factor
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A van den Wijngaard,
P Volders,
J P Van Tintelen,
J D H Jongbloed, M P van den Berg,
R H Lekanne Deprez,
M M A M Mannens,
N Hofmann,
M Slegtenhorst,
D Dooijes,
M Michels,
Y Arens,
R Jongbloed,
B J M Smeets
[show abstract]
[hide abstract]
ABSTRACT: About 2-7% of familial cardiomyopathy cases are caused by a mutation in the gene encoding cardiac troponin I (TNNI3). The related clinical phenotype is usually severe with early onset. Here we report on all currently known mutations in the Dutch population and compared these with those described in literature.
TheTNNI3 gene was screened for mutations in all coding exons and flanking intronic sequences in a large cohort of cardiomyopathy patients. All Dutch index cases carrying a TNNI3 mutation that are described in this study underwent extensive cardiological evaluation and were listed by their postal codes.
In 30 families, 14 different mutations were identified. Three TNNI3 mutations were found relatively frequently in both familial and non-familial cases of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM). Haplotype analysis showed that p.Arg145Trp and p.Ser166Phe are founder mutations in the Netherlands, while p.Glu209Ala is not. The majority of Dutch TNNI3 mutations were associated with a HCM phenotype. Mean age at diagnosis was 36.5 years. Mutations causing RCM occurred less frequently, but were identified in very young children with a poor prognosis.
In line with previously published data, we found TNNI3 mutations to be rare and associated with early onset and severe clinical presentation.
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 05/2011; 19(7-8):344-51. · 1.44 Impact Factor
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P A van der Zwaag,
J P van Tintelen,
F Gerbens,
J D H Jongbloed,
L G Boven,
J J van der Smagt,
W P van der Roest,
I M van Langen,
H Bikker,
R N W Hauer, M P van den Berg,
R M W Hofstra,
G J te Meerman
[show abstract]
[hide abstract]
ABSTRACT: Identifying a mutation in a heterogeneous disease such as inherited cardiomyopathy is a challenge because classical methods, like linkage analysis, can often not be applied as there are too few meioses between affected individuals. However, if affected individuals share the same causal mutation, they will also share a genomic region surrounding it. High-density genotyping arrays are able to identify such regions shared among affected individuals. We hypothesize that the longest shared haplotype is most likely to contain the disease-causing mutation. We applied this method to two pedigrees: one with arrhythmogenic right ventricular cardiomyopathy (ARVC) and one with dilated cardiomyopathy (DCM), using high-density genome-wide SNP arrays. In the ARVC pedigree, the largest haplotype was on chromosome 12 and contained a causative PKP2 mutation. In the DCM pedigree, a causative MYH7 mutation was present on a large shared haplotype on chromosome 14. We calculated that a pedigree containing at least seven meioses has a high chance of correctly detecting the mutation-containing haplotype as the largest. Our data show that haplotype sharing analysis can assist in identifying causative genes in families with low penetrance Mendelian diseases, in which standard tools cannot be used due to lack of sufficient pedigree information.
Clinical Genetics 05/2011; 79(5):459-67. · 3.13 Impact Factor
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P A van der Zwaag,
M G P J Cox,
C van der Werf,
A C P Wiesfeld,
J D H Jongbloed,
D Dooijes,
H Bikker,
R Jongbloed,
A J H Suurmeijer, M P van den Berg,
R M W Hofstra,
R N W Hauer,
A A M Wilde,
J P van Tintelen
[show abstract]
[hide abstract]
ABSTRACT: Background. Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p.Arg79X mutation in PKP2 has been identified in Europe and North America and has been functionally characterised. We evaluated the prevalence of the p.Arg79X mutation in PKP2 in the Dutch population. Methods. Twelve index patients and 41 family members were evaluated in three university hospitals in the Netherlands. The diagnosis of ARVC/D was established according to the recently revised Task Force Criteria. Segregation of the p.Arg79X mutation was studied and haplotypes were reconstructed to determine whether the p.Arg79X mutation was a recurrent or a founder mutation. Results. The p.Arg79X mutation in PKP2 was identified in 12 index patients. Haplotype analysis revealed a shared haplotype among Dutch p.Arg79X mutation carriers, indicating a common founder. Six index patients (50%) had a first- or second-degree relative who had died of sudden cardiac death below 40 years of age. At age 60, only 60% of the mutation carriers had experienced any symptoms. There was no significant difference in symptom-free survival and event-free survival between men and women. Conclusion. We have identified the largest series of patients with the same desmosome gene mutation in ARVC/D reported to date. This p.Arg79X mutation in PKP2 is a founder mutation in the Dutch population. The phenotypes of PKP2 p.Arg79X mutation carriers illustrate the clinical variability and reduced penetrance often seen in ARVC/D. (Neth Heart J 2010;18:583-91.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 11/2010; 18(12):583-91. · 1.44 Impact Factor
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E Otten,
R H Lekanne Dit Deprez,
M M Weiss,
M van Slegtenhorst,
M Joosten,
J J van der Smagt,
N de Jonge,
W S Kerstjens-Frederikse,
M T R Roofthooft,
A H M M Balk, M P van den Berg,
J S Ruiter,
J P van Tintelen
[show abstract]
[hide abstract]
ABSTRACT: Background. About 30% of dilated cardiomyopathy (DCM) cases are familial. Mutations are mostly found in the genes encoding lamin A/C, beta-myosin heavy chain and the sarcomeric protein cardiac troponin-T (TNNT2). Mutations in TNNT2 are reported in approximately 3% of DCM patients. The overall phenotype caused by TNNT2 mutations is thought to be a fully penetrant, severe disease. This also seems to be true for a recurrent deletion in the TNNT2 gene; p.K217del (also known as p.K210del). Methods. We compared the phenotype of all Dutch patients identified as carrying the TNNT2 p.K217del mutation with those described in the literature. All index patients underwent cardiological evaluation. Family screening was done in all described families. Results. Six DCM patients carrying the TNNT2 p.K217del mutation were identified from four Dutch families. Mean age of disease manifestation was 33 years. Heart transplantation was required in three of them at ages 12, 18 and 19 years. These outcomes are comparable with those described in the literature. Conclusion. Carriers of the TNNT2 p.K217del mutation in our Dutch families, as well as in families described in the literature before, generally show a severe, early-onset form of DCM. (Neth Heart J 2010;18:478-85.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 10/2010; 18(10):478-85. · 1.44 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: van Spaendonck-Zwarts KY, van Hessem L, Jongbloed JDH, de Walle HEK, Capetanaki Y, van der Kooi AJ, van Langen IM, van den Berg MP, van Tintelen JP. Desmin-related myopathy: a review and meta-analysis. Desmin-related myopathy (DRM) is an autosomally inherited skeletal and cardiac myopathy, mainly caused by dominant mutations in the desmin gene (DES). We provide (i) a literature review on DRM, including clinical manifestations, inheritance, molecular genetics, myopathology and management and (ii) a meta-analysis of reported DES mutation carriers, focusing on their clinical characteristics and potential genotype-phenotype correlations. Meta-analysis: DES mutation carriers (n = 159) with 40 different mutations were included. Neurological signs were present in 74% and cardiological signs in 74% of carriers (both neurological and cardiological signs in 49%, isolated neurological signs in 22%, and isolated cardiological signs in 22%). More than 70% of carriers exhibited myopathy or muscular weakness, with normal creatine kinase levels present in one third of them. Up to 50% of carriers had cardiomyopathy and around 60% had cardiac conduction disease or arrhythmias, with atrioventricular block as an important hallmark. Symptoms generally started during the 30s; a quarter of carriers died at a mean age of 49 years. Sudden cardiac death occurred in two patients with a pacemaker, suggesting a ventricular tachyarrhythmia as cause of death. The majority of DES mutations were missense mutations, mostly located in the 2B domain. Mutations in the 2B domain were predominant in patients with an isolated neurological phenotype, whereas head and tail domain mutations were predominant in patients with an isolated cardiological phenotype.
Clinical Genetics 07/2010; · 3.13 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Background/Methods. Marfan syndrome (MFS) is a heritable connective tissue disorder usually caused by a mutation in the fibrillin 1 (FBN1) gene. Typical characteristics of MFS that have been described include dolichostenomelia, ectopia lentis and aortic root dilatation. However, there is great clinical variability in the expression of the syndrome's manifestations, both between and within families. Here we discuss the clinical variability of MFS by describing a large fourgeneration Dutch family with MFS.Results. Nineteen individuals of one family with a single missense FBN1 mutation (c.7916A>G) were identified. The same mutation was found in one unrelated person. Clinical variability was extensive and not all mutation carriers fulfilled the diagnostic criteria for MFS. Some patients only expressed mild skeletal abnormalities, whereas aortic root dilation was present in eight patients, an acute type A aortic dissection was recorded in two other patients, and a mitral valve prolapse was present in eight patients. In some patients cardiac features were not present on initial screening, but did however develop over time.Conclusion. MFS is a clinically highly variable syndrome, which means a meticulous evaluation of suspected cases is crucial. Mutation carriers should be re-evaluated regularly as cardiovascular symptoms may develop over time. (Neth Heart J 2010;18:85-9.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 02/2010; 18(2):85-9. · 1.44 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Background. The results of acute type A dissection (AAD) surgery in the Netherlands are largely unknown, as was recently stated in a report by the Health Council of the Netherlands. In order to gain more insight into the Dutch situation we investigated predictors of in-hospital mortality of surgically treated AAD patients and assessed threeyear survival.Methods. 104 consecutive patients undergoing surgery for AAD in a 16-year period (1990-2006) were evaluated. Preoperative and intraoperative variables were analysed to identify predictors of early mortality.Results. Preoperative malperfusion (limb ischaemia or mesenteric ischaemia) was present in 15.4%, shock in 18.3%, and 6.7% were operated under cardiac massage. Marfan syndrome was present in four patients and four patients had a bicuspid aortic valve. In-hospital mortality was 22.1%. Seven patients died intraoperatively; other causes of inhospital mortality were major brain damage in ten patients, multiple organ failure in three patients, low cardiac output in two patients and sudden cardiac death in one patient. Multivariate logistic regression revealed preoperative malperfusion (p=0.004) to be the only independent predictor of in-hospital mortality. Three-year survival was 68.8+/-4.7% (including hospital mortality). Hospital survivors had a three-year survival of 88.3+/-3.9%.Conclusion. In-hospital mortality of our patients (22.1%) is comparable with the results of larger case series published in the literature. Prognosis after successful surgical treatment is relatively good with a three-year survival of 88.3% in our series. (Neth Heart J 2009;17:226-31.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 06/2009; 17(6):226-31. · 1.44 Impact Factor
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[show abstract]
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ABSTRACT: Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients.Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA.Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA.Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232-7.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 06/2009; 17(6):232-7. · 1.44 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Long-term cardiovascular morbidity is increasingly observed in chemotherapy-treated testicular cancer survivors, but little is known of early sub-clinical changes in cardiac function. We prospectively evaluated cardiac function in testicular cancer patients by echocardiography. Systolic (Wall Motion Score Index) and diastolic (E/A-ratio and Tissue Velocity Imaging (TVI)) parameters, and serum levels of N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) were assessed before the start of chemotherapy and 1 year later. Echocardiography data were compared with an age-matched group of healthy controls. Forty-two patients treated with bleomycin, etoposide and cisplatin were evaluated (median age 27 years, range 18-50). Systolic function and E/A-ratio did not change, whereas the median TVI decreased (12.0 vs 10.0 cms(-1); P=0.002). Median levels of NT-proBNP increased (5 vs 18 pmoll(-1), P=0.034). Compared with controls, TVI before the start of chemotherapy was not significantly different. In conclusion, we found that at a median of 10 months after cisplatin-based treatment for testicular cancer, TVI decreased significantly, indicating a deterioration of diastolic cardiac function. Serum levels of NT-proBNP increased. The prognostic significance of these changes for future cardiovascular morbidity is not clear.
British Journal of Cancer 06/2009; 100(12):1861-6. · 5.04 Impact Factor
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Circulation. 01/2009; 120(18):S555-S556.
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ABSTRACT: Loeys-Dietz syndrome (LDS) is a newly recognised disorder of connective tissue which shares overlapping features with Marfan syndrome (MFS) and the vascular type of Ehlers-Danlos syndrome, including aortic root dilatation and skin abnormalities. It is clinically classified into types 1 and 2. LDS type 1 can be recognised by craniofacial characteristics, e.g. hypertelorism, bifid uvula or cleft palate, whereas these are absent in LDS type 2. It is important to recognise LDS because its vascular pathology is aggressive. We describe nine LDS patients from four families, relate their features to published cases, and discuss important aspects of the diagnosis and management of LDS in order to make clinicians aware of this new syndrome.
Characteristics found in the majority of these LDS patients were aortic root dilatation, cleft palate and/or a bifid/abnormal uvula.
Because aortic dissection and rupture in LDS tend to occur at a young age or at aortic root diameters not considered at risk in MFS, and because the vascular pathology can be seen throughout the entire arterial tree, patients should be carefully followed up and aggressive surgical treatment is mandatory. Clinicians must therefore be aware of LDS as a cause of aggressive aortic pathology and that its distinguishing features can sometimes be easily recognised. (Neth Heart J 2008;16:299-304.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 10/2008; 16(9):299-304. · 1.44 Impact Factor
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[show abstract]
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ABSTRACT: B-type natriuretic peptide (BNP) is secreted from cardiomyocytes and may reflect haemodynamic abnormalities predisposing to atrial fibrillation (AF). We aimed to investigate whether N-terminal pro BNP (NT-proBNP) is associated with newly detected AF in subjects obtained from the general population.
From the PREVEND programme (n=8592), we selected all subjects with an available baseline and four-year electrocardiogram and NTproBNP levels at baseline. We excluded subjects with AF at baseline and subjects with a serum creatinine >2.0 mg/dl.
In total, 6494 subjects were eligible for the prospective analysis (aged 49+/-12 years, 49.7% men). At four years, AF was detected in 41 (0.6%) subjects. Median NT-proBNP levels at baseline in subjects with newly detected AF after four years was 62.2 (22.6 to 208.5) pg/ml as compared with 35.7 (15.9 to 68.7) pg/ml in those with sinus rhythm (p=0.001). Each 1 standard deviation increment in natural log transformed NT-proBNP was associated with a 54% (5% to 126%, p=0.028) increase in risk for AF after adjustment for other risk factors predisposing to AF. NT-proBNP levels above the sex-specific 80th percentile (97 pg/ml in women and 60 pg/ml in men) were associated with a multivariate odds ratio of 2.65 (1.22 to 5.76, p=0.01) for the occurrence of AF.
Plasma levels of NT-proBNP predict newly detected AF in subjects obtained from the general population independent of cardiovascular risk factors predisposing to AF. (Neth Heart J 2008;16:73-8.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 03/2008; 16(3):73-8. · 1.44 Impact Factor
