TY - JOUR AU - Oijen, M.G.H. van AU - Koetsier, M.I.A. AU - Laheij, R.J.F. AU - Roelofs, H.M.J. AU - Morsche, R.H.M. te AU - Peters, W.H.M. AU - Verheugt, F.W.A. AU - Jansen, J.B.M.J. AU - Drenth, J.P.H. PY - 2009 UR - https://hdl.handle.net/2066/80620 AB - UDP-glucuronosyltransferase 1A6 (UGT1A6) is involved in metabolizing non-steroidal anti-inflammatory drugs (NSAIDs). Genotype variation in UGT1A6 may influence the metabolism of NSAIDs and we studied whether this might modulate the gastrointestinal toxicity of NSAIDs. UGT1A6 genotypes of 114 patients with peptic ulcer haemorrhage were compared with those of two subsets of controls: 158 cardiology patients using similar amounts of NSAIDs and 140 healthy controls, hardly using NSAIDs. Risk factors for peptic ulcer bleeding were male gender (Odds ratio (OR) 2.66, 95% confidence interval (CI) 1.7-4.2), age above 60 years (OR 2.15, 95% CI 1.4-3.4) and use of NSAIDs/aspirin (OR 4.50, 95% CI 2.8-7.3). UGT1A6 genotype frequencies did not differ between patients with peptic ulcer and the two control groups (p=0.76). We conclude that polymorphic UGT1A6 is not implicated in the pathogenesis of NSAIDs-related peptic ulcer disease. TI - Genetic polymorphisms in UDP-glucuronosyltransferase 1A6 are not associated with NSAIDs-related peptic ulcer haemorrhage. EP - 204 SN - 1872-3128 IS - iss. 3 SP - 199 JF - Drug Metabolism Letters VL - vol. 3 ER - TY - JOUR AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/79519 TI - Acute myocardial infarction associated with ST segment elevation and the new European Society of Cardiology guidelines. EP - 1117 SN - 1355-6037 SP - 1112 JF - Heart VL - vol. 95 DO - http://dx.doi.org/10.1136/hrt.2008.151829 ER - TY - THES AU - Werkum, J.W. van PY - 2009 SN - 9789090238111 UR - https://hdl.handle.net/2066/79499 PB - [S.l. : s.n.] TI - Platelets and Stent Thrombosis. N1 - RU Radboud Universiteit Nijmegen, 9 januari 2009 N1 - Promotor : Verheugt, F.W.A. Co-promotores : Berg, J.M. ten, Hackeng, C.M. PS - 270 p. ER - TY - THES AU - Kievit, P.C. PY - 2009 SN - 9789090240435 UR - https://hdl.handle.net/2066/74387 PB - [S.l. : s.n.] TI - Predictors of reocclusion and clinical outcome after succesful fibrinolysis. N1 - RU Radboud Universiteit Nijmegen, 20 maart 2009 N1 - Promotor : Verheugt, F.W.A. Co-promotor : Brouwer, M.A. PS - 190 p. L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/74387/74387.pdf?sequence=1 ER - TY - JOUR AU - Camaro, C. AU - Aengevaeren, W.R.M. PY - 2009 UR - https://hdl.handle.net/2066/79511 AB - A 66-year-old female was referred for primary coronary intervention because of acute inferior STelevation myocardial infarction. Electrocardiography also showed atrial fibrillation. Coronary angiography showed a distal occlusion of the right coronary artery. Two different wires did not pass the occlusion, but dislodged the apparent thrombus more distally. No abnormalities were seen in the course of the recanalised part of the vessel. The sequential angiographic images together with the presence of atrial fibrillation are highly suggestive of coronary embolism as the cause of the myocardial infarction. Anticoagulation and rate control strategy was initiated. The patient was discharged in good condition. (Neth Heart J 2009;17:297-9.). TI - Acute myocardial infarction due to coronary artery embolism in a patient with atrial fibrillation. EP - 299 SN - 1568-5888 IS - iss. 7-8 SP - 297 JF - Netherlands Heart Journal VL - vol. 17 DO - http://dx.doi.org/10.1007/BF03086271 ER - TY - JOUR AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/79836 TI - Who is ineligible for warfarin in atrial fibrillation EP - 511 SN - 0140-6736 IS - iss. 9689 SP - 510 JF - The Lancet (London) VL - vol. 374 DO - http://dx.doi.org/10.1016/S0140-6736(09)61471-9 ER - TY - JOUR AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/80293 TI - In seach of a better thienopyridine for PCI EP - 189 SN - 1568-5888 SP - 188 JF - Netherlands Heart Journal VL - vol. 17 ER - TY - JOUR AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/81650 TI - Routine angioplasty after fibrinolysis: how early should "early" be? EP - 2281 SN - 0028-4793 IS - iss. 26 SP - 2779 JF - The New England Journal of Medicine VL - vol. 360 DO - http://dx.doi.org/10.1056/NEJMe0902460 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/81650/81650.pdf?sequence=1 ER - TY - JOUR AU - Panhuyzen-Goedkoop, N.M. PY - 2009 UR - https://hdl.handle.net/2066/81910 TI - Preparticipation cardiovascular screening in young athletes. EP - 630 SN - 0306-3674 IS - iss. 9 SP - 629 JF - British Journal of Sports Medicine VL - vol. 43 DO - http://dx.doi.org/10.1136/bjsm.2009.064220 ER - TY - JOUR AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/81696 TI - Reperfusion therapy: trials, registries and guidelines EP - 3049 SN - 0009-7322 IS - iss. 24 SP - 3047 JF - Circulation VL - vol. 119 DO - http://dx.doi.org/10.1161/CIRCULATIONAHA.109.873778 ER - TY - JOUR AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/80911 TI - Dotteren bij stabiele angina pectoris: niet kosteneffectief vergeleken met medicamenteuze behandeling J2 - [Percutaneous coronary intervention in stable angina pectoris. Not cost-effective on comparison with medical treatment] EP - A128 SN - 0028-2162 SP - A128 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 153 ER - TY - JOUR AU - Etten, J. van AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/79763 AB - In a 55-year-old woman and a 51-year-old man with an ST segment elevation myocardial infarction confirmed by ECG, the infarction could still be aborted by percutaneous coronary intervention with stenting. An aborted myocardial infarction can be described as an acute myocardial infarction in which rapid reperfusion therapy allows normalization of ECG abnormalities with no meaningful cardiac enzyme abnormalities found in the blood. Scientific evidence shows fibrinolysis to be effective in aborting myocardial infarction, but for percutaneous coronary intervention this has not been proven. Nevertheless, the results of the 2 cases discussed in our article are promising. TI - [Myocardial infarction aborted by rapid percutaneous coronary intervention] J2 - [Myocardial infarction aborted by rapid percutaneous coronary intervention] EP - A467 SN - 0028-2162 SP - A467 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 153 ER - TY - JOUR AU - Bode, C. AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/81221 TI - The need for new oral anticoagulants in clinical practice: an introduction. EP - 594 SN - 1558-2027 IS - iss. 8 SP - 593 JF - Journal of Cardiovascular Medicine VL - vol. 10 DO - http://dx.doi.org/10.2459/JCM.0b013e32832e48f8 ER - TY - JOUR AU - Camaro, C. AU - Derksen, R. AU - Smeets, J.L.R.M. PY - 2009 UR - https://hdl.handle.net/2066/81605 TI - Origin of monomorphic broad QRS tachycardia EP - 403 SN - 1568-5888 SP - 398 JF - Netherlands Heart Journal VL - vol. 17 ER - TY - JOUR AU - Draisma, A. AU - Goeij, M. de AU - Wouters, C.W. AU - Riksen, N.P. AU - Oyen, W.J.G. AU - Rongen, G.A.P.J.M. AU - Boerman, O.C. AU - Deuren, M. van AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/80768 AB - Animal studies have shown that previous exposure to lipopolysaccharide (LPS) can limit ischemia-reperfusion injury. We tested whether pretreatment with LPS also protects against ischemia-reperfusion injury in humans in vivo. Fourteen volunteers received bolus injections of incremental dosages of LPS on 5 consecutive days (LPS group). Before the first and 1 day after the last LPS administration, the forearm circulation of the non-dominant arm was occluded for 10 min, with concomitant intermittent handgripping to induce transient ischemia. After reperfusion, 0.1 mg of ( 99m)Tc-labeled annexin A5 (400 MBq) was injected intravenously to detect phosphatidylserine expression as an early marker of ischemia-reperfusion injury. Similarly, the control group (n = 10) underwent the ischemic exercise twice, but without pretreatment with LPS. Annexin A5 targeting was expressed as the percentage difference in radioactivity in the thenar muscle between both hands. Endotoxin tolerance developed during 5 consecutive days of LPS administration. Annexin A5 targeting was 12.1 +/- 2.2% and 10.4 +/- 2.1% before LPS treatment at 1 h and 4 h after reperfusion, compared to 12.2 +/- 2.4% and 8.9 +/- 2.1% at 1 h and 4 h after reperfusion on day 5 (P = 1.0 and 0.6, respectively). Also, no significant changes in annexin A5 targeting were found in the control group. So, in this model, LPS-tolerance does not protect against ischemia-reperfusion injury in humans in vivo. TI - Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo. EP - 367 SN - 1753-4259 IS - iss. 6 SP - 360 JF - Innate Immunity VL - vol. 15 DO - http://dx.doi.org/10.1177/1753425909105548 ER - TY - JOUR AU - Camaro, C. AU - Danse, P.W. AU - Bosker, H.A. PY - 2009 UR - https://hdl.handle.net/2066/79518 AB - A 61-year-old male with a history of metastatic colorectal cancer was referred to our hospital for primary coronary intervention because of acute ST-elevation myocardial infarction. Coronary angiography, however, revealed no significant stenoses. When asked, the patient revealed that capecitabine (Xeloda(R)) was started by his oncologist one day before admission. It is known that this oral 5-FU analogue drug, used in metastatic colorectal cancer, can cause coronary artery spasms. The main treatment of capecitabine-induced vasospasm is discontinuation of the drug. Indeed, after cessation of the drug the patient remained free of symptoms and the ECG abnormalities normalised. (Neth Heart J 2009;17:288-91.). TI - Acute chest pain in a patient treated with capecitabine. EP - 291 SN - 1568-5888 IS - iss. 7-8 SP - 288 JF - Netherlands Heart Journal VL - vol. 17 ER - TY - JOUR AU - Roos, M. AU - Sarkozy, A. AU - Chierchia, G.B. AU - Wilde, P.C.M. de AU - Schmedding, E. AU - Brugada, P. PY - 2009 UR - https://hdl.handle.net/2066/79893 AB - We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration and frequency. An electrophysiological study revealed prolonged His-ventricular (HV) interval duration and induction of sustained ventricular tachycardia. The patient was successfully upgraded to a prophylactic dual-chamber cardioverter defibrillator. Our case is the first description of a patient with adult-onset SMA (Kugelberg-Welander disease [KWD]) and malignant ventricular arrhythmias. TI - Malignant ventricular arrhythmia in a case of adult onset of spinal muscular atrophy (Kugelberg-Welander disease). EP - 344 SN - 1045-3873 IS - iss. 3 SP - 342 JF - Journal of Cardiovascular Electrophysiology VL - vol. 20 DO - https://doi.org/10.1111/j.1540-8167.2008.01327.x ER - TY - JOUR AU - Rolink, A.M. AU - Verheugt, F.W.A. AU - Bosker, H.A. PY - 2009 UR - https://hdl.handle.net/2066/80275 AB - BACKGROUND: Cardiac resynchronisation therapy (CRT) is an effective treatment to improve the clinical outcome of selected patients with heart failure. Clinical trials have studied clinical outcome and reported clinical improvements, but clinical consequences and results in daily practice are less well known. We evaluated clinical outcome in all patients with CRT implantation in our centre. METHODS: Data of 119 consecutive patients who met the criteria for CRT implantation in Rijnstate Hospital, Arnhem in the period 28 November 2000 until 1 January 2006 were collected. We analysed implantation procedure, hospitalisation for heart failure or other causes, mortality and device-related events. RESULTS: In total 119 patients (83 men, 36 women; mean age 69 years) were eligible for CRT. Before implantation they had received optimal pharmacological therapy. Implantation was successful in 97% of patients. Procedural-related complications were seen in eight patients. During follow-up, 22 patients (18.5%: 14 men, 8 women) died. Causes of death were heart failure (11 patients), sudden cardiac death (4 patients) and noncardiac death (7 patients). Hospitalisation occurred 81 times, of which 77 for cardiac reasons. In follow-up the estimated five-year cumulative survival was 70%. CONCLUSION: This retrospective study from a single centre showed a high procedural success rate, low prevalence of complications and low mortality in comparison to other studies. Despite better functional capacity, the hospitalisation rate due to heart failure was high. (Neth Heart J 2009;17:6-8.). TI - Cardiac resynchronisation therapy: results from daily practice in Rijnstate Hospital, Arnhem. EP - 8 SN - 1568-5888 IS - iss. 1 SP - 6 JF - Netherlands Heart Journal VL - vol. 17 ER - TY - JOUR AU - Kaplan, E. AU - Min, J.Y. AU - Ke, Q. AU - Chen, Y. AU - Niethammer, M. AU - Rana, J.S. AU - Malek, S. AU - Verheugt, F.W.A. AU - Morgan, J.P. PY - 2009 UR - https://hdl.handle.net/2066/80403 AB - The purpose of this study was to study the effect of calcium, cyclic AMP (cAMP) and cyclic GMP (cGMP) on embryonic stem cell (ESC) motility during TNF-alpha-induced chemotaxis. ESCs were monitored using a chemotaxis chamber, with different concentrations of calcium or cAMP or cGMP added to the medium. Changes in intracellular calcium ([Ca(2+)](i)) were measured with the fluorescent dye fura-2/AM. We combined migratory parameters in a mathematical model and described it as "mobility". After adding calcium, a dose-dependant increase in cell speed was found. Cyclic AMP increased mobility as well as the [Ca(2+)](i). In contrast, adding dbcGMP resulted in a significant decrease in the mobility of the ESCs. During migration ESCs showed an increase in [Ca(2+)](i). Furthermore, TNF-alpha dramatically increased the movement as well as the directionality of ESCs. These results demonstrate that ESCs are highly motile and respond to different concentrations of calcium in a dose-related manner. TI - Calcium and cyclic nucleotides affect TNF-alpha-induced stem cell migration. EP - 246 SN - 0006-291X IS - iss. 2 SP - 241 JF - Biochemical and Biophysical Research Communications VL - vol. 382 DO - https://doi.org/10.1016/j.bbrc.2009.02.068 ER - TY - JOUR AU - Vonk, M.C. AU - Broers, B. AU - Heijdra, Y.F. AU - Ton, E. AU - Snijder, R. AU - Dijk, A.P.J. van AU - Laar, J.M. van AU - Bootsma, H.J. AU - Hal, P.T. van AU - Hoogen, F.H.J. van den AU - Daele, P.L. van PY - 2009 UR - https://hdl.handle.net/2066/81439 AB - The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. OBJECTIVE: To establish the prevalence and incidence of SSc and its pulmonary complications. METHODS: Detailed information on patients in the POEMAS registry, "Pulmonary Hypertension Screening, a Multidisciplinary Approach in Scleroderma", consisting of 819 patients, was combined with a nationwide questionnaire. RESULTS: By combining the two sources the prevalence of SSc was found to be 8.9 per 100 000 adults. The incidence was 0.77 patients per 100 000 per year. PAH was diagnosed in 9.9% of SSc patients. The prevalence of interstitial lung disease in SSc varied from 19% to 47% depending on the definition used. CONCLUSION: This study clarifies the epidemiology of SSc in The Netherlands and confirms the frequent occurrence of pulmonary complications, based on 654 cases. This can and will be studied further in the ongoing POEMAS study. TI - Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study. EP - 965 SN - 0003-4967 IS - iss. 6 SP - 961 JF - Annals of the Rheumatic Diseases VL - vol. 68 DO - https://doi.org/10.1136/ard.2008.091710 ER - TY - JOUR AU - Dijk, F.S. Van AU - Hamel, B.C.J. AU - Hilhorst-Hofstee, Y. AU - Mulder, B.J. AU - Timmermans, J. AU - Pals, G. AU - Cobben, J.M. PY - 2009 UR - https://hdl.handle.net/2066/81680 AB - We report two families in which the probands have compound-heterozygous Marfan syndrome (MFS). The proband of family 1 has the R2726W FBN1 mutation associated with isolated skeletal features on one allele and a pathogenic FBN1 mutation on the other allele. The phenotype of the compound-heterozygous probands appears to be more severe than that of their heterozygous family members which underlines the possibility that certain trans-located FBN1 mutations might act as modifiers of phenotype explaining some of the intrafamilial variability in Marfan syndrome. TI - Compound-heterozygous Marfan syndrome. EP - 5 SN - 1769-7212 IS - iss. 1 SP - 1 JF - European Journal of Medical Genetics VL - vol. 52 DO - https://doi.org/10.1016/j.ejmg.2008.11.004 ER - TY - JOUR AU - Duffels, M.G. AU - Plas, M.N. van der AU - Surie, S. AU - Winter, M.M. AU - Bouma, B. AU - Groenink, M. AU - Dijk, A.P.J. van AU - Hoendermis, E.S. AU - Berger, R.M. AU - Bresser, P. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/80796 AB - Background. In patients with pulmonary hypertension, it is unknown whether the treatment effect of bosentan is dependent on the duration of pulmonary vessel changes. Therefore, we studied the response to bosentan in patients with life-long pulmonary vessel changes (pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD)) and in patients with subacutely induced pulmonary vessel changes (chronic thromboembolic pulmonary hypertension (CTEPH)).Methods. In this open-label study, 18 patients with PAH due to CHD and 16 patients with CTEPH were treated with bosentan for at least one year. All patients were evaluated at baseline and during follow-up by means of the six-minute walk distance (6-MWD) and laboratory tests.Results. Improvement of 6-MWD was comparable in patients with PAH due to CHD (444+/-112 m to 471+/-100 m, p=0.02), and in CTEPH (376+/-152 m to 423+/-141 m, p=0.03) after three months of treatment. After this improvement, 6-MWD stabilised in both groups.Conclusion. Although duration of pulmonary vessel changes is strikingly different in patients with PAH due to CHD and CTEPH, the effect of one year of bosentan treatment was comparable. The main treatment effect appears to be disease stabilisation and decreasing the rate of deterioration. (Neth Heart J 2009;17:334-8.). TI - Bosentan in pulmonary arterial hypertension: a comparison between congenital heart disease and chronic pulmonary embolism. EP - 338 SN - 1568-5888 IS - iss. 9 SP - 334 JF - Netherlands Heart Journal VL - vol. 17 DO - https://doi.org/10.1007/BF03086279 ER - TY - JOUR AU - Duffels, M.G. AU - Vis, J.C. AU - Loon, R.L. van AU - Nieuwkerk, P.T. AU - Dijk, A.P.J. van AU - Hoendermis, E.S. AU - Bruin-Bon, R.H. de AU - Bouma, B.J. AU - Bresser, P. AU - Berger, R.M. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/80845 AB - Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study, the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease, including patients with Down's syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests, 6-minute walk test, QoL questionnaires, and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Down's syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Down's syndrome, mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment, followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Down's syndrome, 6-minute walk distance and QoL were stable during treatment. In conclusion, findings suggested that in patients without Down's syndrome, longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity. TI - Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome. EP - 1315 SN - 0002-9149 IS - iss. 9 SP - 1309 JF - American Journal of Cardiology VL - vol. 103 DO - https://doi.org/10.1016/j.amjcard.2009.01.021 ER - TY - JOUR AU - Duffels, M.G. AU - Vis, J.C. AU - Loon, R.L. van AU - Berger, R.M. AU - Hoendermis, E.S. AU - Dijk, A.P.J. van AU - Bouma, B.J. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/80912 AB - BACKGROUND: Favorable results of treatment with bosentan in patients with Eisenmenger syndrome are available. However, data in Down patients are lacking. In this study, we evaluate the therapeutic role of bosentan treatment in Down patients with Eisenmenger syndrome. METHODS: In this open-label study, 24 Down patients (>18 years) with Eisenmenger syndrome (17 males) were treated with bosentan. Their mean age was 38 years (range 19-55 years). All Down patients were evaluated at baseline and during follow-up with laboratory tests, six-minute walk test (6-MWT), Doppler echocardiography, and quality of life questionnaires. RESULTS: The median follow-up of Down patients treated with bosentan was 11.5 months (range 3-23 months). Induction of oral bosentan therapy was well tolerated among all 24 Down patients. Bosentan treatment was generally well tolerated. No serious adverse drug reactions were noted. Median 6-MWT increased from 296 m (range 40-424 m) to 325 m (range 84-459 m, p<0.05) after 12 weeks. After 26 and 52 weeks of treatment with bosentan, median 6-MWT distance was 276 m (range 140-462 m, n=15, p=0.6) and 287 m (range 131-409 m, n=7, p=0.3), respectively. Quality of life questionnaire scores remained stable during treatment. CONCLUSION: Also patients with Down syndrome may benefit from bosentan treatment when they have Eisenmenger syndrome. Medical treatment appears to be safe and the treatment effects do not deviate from those observed in Eisenmenger patients without Down syndrome. TI - Down patients with Eisenmenger syndrome: Is bosentan treatment an option? EP - 383 SN - 0167-5273 IS - iss. 3 SP - 378 JF - International Journal of Cardiology VL - vol. 134 DO - https://doi.org/10.1016/j.ijcard.2008.02.025 ER - TY - JOUR AU - Duffels, M.G. AU - Hardziyenka, M. AU - Surie, S. AU - Bruin-Bon, R.H. de AU - Hoendermis, E.S. AU - Dijk, A.P.J. van AU - Bouma, B.J. AU - Tan, H.L. AU - Berger, R.M. AU - Bresser, P. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/80922 AB - AIMS: In patients with pulmonary hypertension (PH), elevated endothelin-1 levels are associated with prolonged duration of right ventricular (RV) contraction, which induces leftward ventricular septal bowing with impaired left diastolic filling. We hypothesized that baseline RV contraction duration predicts efficacy of endothelin receptor antagonist, bosentan. METHODS AND RESULTS: Eighteen PH patients (age 57, range 35-79 years, 33% male) received bosentan. Six minute walk distance (6-MWD) and echocardiography were performed at baseline and after 1 year follow-up. After 1 year of treatment, 6-MWD increased (mean 60 +/- 41 m) in 67% of patients (responders). Baseline RV contraction duration was longer in responders, compared with non-responders (612 +/- 66 vs. 514 +/- 23 ms; P < 0.01). A baseline RV contraction duration >550 ms was associated with improved 6-MWD (sensitivity 83%, specificity 83%; P < 0.01). CONCLUSION: An improvement of 6-MWD during bosentan treatment was associated with a decrease in RV contraction duration and could be predicted by a baseline RV contraction duration >550 ms. TI - Duration of right ventricular contraction predicts the efficacy of bosentan treatment in patients with pulmonary hypertension. EP - 438 SN - 1525-2167 IS - iss. 3 SP - 433 JF - European Journal of Echocardiography VL - vol. 10 DO - https://doi.org/10.1093/ejechocard/jen308 ER - TY - JOUR AU - Vis, J.C. AU - Thoonsen, H. AU - Duffels, M.G. AU - Bruin-Bon, R.A. de AU - Huisman, S.A. AU - Dijk, A.P.J. van AU - Hoendermis, E.S. AU - Berger, R.M. AU - Bouma, B.J. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/81543 AB - OBJECTIVES: To examine the validity of the six-minute walk test (6MWT) as a tool to evaluate functional exercise performance in patients with Down syndrome (DS). DESIGN: Comparison of the six-minute walk distance (6MWD) in 2 distinct groups of DS patients: with and without severe cardiac disease. To test reproducibility, a group of patients with DS performed the 6MWT twice. SETTING: Tertiary referral centers for patients with congenital heart defects and outpatient clinics for people with intellectual disabilities. PARTICIPANTS: Adult patients with DS with (n=29) and without (n=52) severe cardiac disease categorized by cardiac echocardiography. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Distance walked on the 6MWT. RESULTS: The mean 6MWD in the group with severe cardiac disease was 289+/-104 m and in the group without severe cardiac disease 280+/-104 m (P=.70). Older age, female sex, and severe level of intellectual disability were all found to be independently and significantly correlated with a lower 6MWD (r=.67, P<.001). The paired 6MWD was not significantly different (310+/-88 m vs 317+/-85 m; P=.40) in patients who performed the 6MWT twice. The coefficient of variation was 11%. CONCLUSIONS: The 6MWD between the 2 groups was not significantly different. However, the walking distance inversely correlated with the level of intellectual disability. Therefore, the 6MWT is not a valid test to examine cardiac restriction in adult patients with DS. TI - Six-minute walk test in patients with Down syndrome: validity and reproducibility. EP - 1427 SN - 0003-9993 IS - iss. 8 SP - 1423 JF - Archives of Physical Medicine and Rehabilitation VL - vol. 90 DO - https://doi.org/10.1016/j.apmr.2009.02.015 ER - TY - JOUR AU - Enajat, M. AU - Teerenstra, S. AU - Kuilenburg, J.T. van AU - Sorge-Greve, A.H. van AU - Albers-Akkers, M.T. AU - Verheugt, F.W.A. AU - Pop, G.A.M. PY - 2009 UR - https://hdl.handle.net/2066/81622 AB - BACKGROUND: The incidence of atrial fibrillation (AF) is very high in the elderly, and often oral anticoagulation (OAC) is indicated to prevent thromboembolism. OBJECTIVE: The aim of this study was to evaluate the safety of combining intensive cholesterol-lowering therapy with OAC in elderly patients with AF. METHODS: In a randomized, double-blind trial, 34 patients received OAC plus atorvastatin 40 mg/day and ezetimibe 10 mg/day versus placebo over 1 year. Dose adjustments of OAC served as an indicator of an interaction between HMG-CoA reductase inhibitors (statins) and OAC. Safety was evaluated by the occurrence of bleeding and a rise in AST, ALT and creatine phosphokinase. RESULTS: Compared with a 6-month pre-intervention period, the mean daily dose +/- standard error of OAC was 4.4 +/- 1.5% lower in the treatment group (p = 0.003) and virtually the same in the placebo group (change from baseline: -0.1 +/- 1.3%, p = 0.96). The mean daily dose of OAC stabilized after 3 months. In the 6-month post-intervention period, OAC dosing showed no statistically significant change from baseline: -1.9 +/- 1.9% in the placebo arm and -2.6 +/- 2.1% in the intervention arm. CONCLUSION: We conclude that in elderly AF patients treated with OAC, intensive cholesterol-lowering therapy (atorvastatin 40 mg/day and ezetimibe 10 mg/day) is well tolerated. No increased risk in bleeding was found. TI - Safety of the combination of intensive cholesterol-lowering therapy with oral anticoagulation medication in elderly patients with atrial fibrillation: a randomized, double-blind, placebo-controlled study. EP - 593 SN - 1170-229X IS - iss. 7 SP - 585 JF - Drugs & Aging VL - vol. 26 DO - https://doi.org/10.2165/10558450-000000000-00000 ER - TY - JOUR AU - Bergh, P.J.P.C. van den AU - Kievit, P.C. AU - Brouwer, M.A. AU - Aengevaeren, W.R.M. AU - Veen, G. AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/81815 AB - BACKGROUND: Long-term addition of antithrombotics (clopidogrel, anticoagulants) to aspirin has improved outcome after acute coronary syndromes. Data on the impact after fibrinolysis are scarce. In Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis-2 (APRICOT-2), adjunctive moderate-intensity coumarin (median international normalized ratio 2.6) conferred a marked reduction in 3-month reocclusion and ischemic events. Given the association between reocclusion and long-term outcome, we performed long-term clinical follow-up. METHODS: Patients with thrombolysis in myocardial infarction (TIMI) 3 flow <48 hours after fibrinolysis for ST-elevation myocardial infarction were randomized to aspirin plus coumarin, with prolonged heparinization until the target international normalized ratio (2-3) was reached, or aspirin with standard heparinization. Three-month follow-up angiography (reocclusion rates 15% vs 28%) and long-term clinical follow-up (median 7.3 years, interquartile range 5.9-8.6 years) were performed. RESULTS: Patients randomized to adjunctive anticoagulation (n = 123) received coumarin for a median of 280 days (113-387 days). Survival was 94% versus 88% in patients on aspirin alone (n = 128, P = .12). Infarct-free survival was 86% versus 71% (P = .01). Thrombolysis in myocardial infarction bleeding was 4% in both groups. Patients with reocclusion had impaired survival: 80% versus 94% (P < .01). In a multivariable model without reocclusion, combination therapy independently predicted survival (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.13-1.00) and infarct-free survival (HR 0.51, 95% CI 0.28-0.95). When adjusted for reocclusion, combination therapy did not predict outcome. Reocclusion independently predicted death (HR 2.56, 95% CI 1.02-6.43) and reinfarction. CONCLUSIONS: Moderate-intensity oral anticoagulation added to aspirin improved 8-year clinical outcome after successful fibrinolysis. The beneficial effect was largely attributed to a reduction in reocclusion, which independently predicted death and reinfarction. This study provides a mechanistic rationale for prolonged adjunctive anticoagulation after fibrinolysis. TI - Prolonged anticoagulation therapy adjunctive to aspirin after successful fibrinolysis: from early reduction in reocclusion to improved long-term clinical outcome. EP - 540 SN - 0002-8703 IS - iss. 3 SP - 532 JF - American Heart Journal VL - vol. 157 DO - https://doi.org/10.1016/j.ahj.2008.11.008 ER - TY - JOUR AU - Velden, L.B. van der AU - Otterspoor, L.C. AU - Schultze Kool, L.J. AU - Biessels, G.J. AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/79510 AB - An acute myocardial infarction is a rare complication of a subarachnoid haemorrhage. The combination of these two conditions imposes important treatment dilemmas. We describe two patients with this combination of life-threatening conditions. Patient 1 was treated with emergency percutaneous coronary intervention followed by clipping of the anterior communicating artery aneurysm. Six months after discharge the patient's memory and orientation had almost completely recovered. Patient 2 was treated with aspirin until coiling of the aneurysm could be performed. After successful coiling low-molecular-weight heparin was added. One week later the patient died due to a free wall rupture. (Neth Heart J 2009;17:284-7.). TI - Acute myocardial infarction complicating subarachnoid haemorrhage. EP - 287 SN - 1568-5888 IS - iss. 7-8 SP - 284 JF - Netherlands Heart Journal VL - vol. 17 ER - TY - JOUR AU - Nieman, A.E. AU - Mast, Q. de AU - Roestenberg, M. AU - Wiersma, J. AU - Pop, G.A.M. AU - Stalenhoef, A.F.H. AU - Druilhe, P. AU - Sauerwein, R.W. AU - Ven, A.J.A.M. van der PY - 2009 UR - https://hdl.handle.net/2066/80283 AB - A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear. TI - Cardiac complication after experimental human malaria infection: a case report. EP - 277 SN - 1475-2875 SP - 277 JF - Malaria Journal VL - vol. 8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/80283/80283.pdf?sequence=1 ER - TY - JOUR AU - Brouwer, J.L.P. AU - Lijfering, W.M. AU - Kate, M.K. Ten AU - Kluin-Nelemans, H.C. AU - Veeger, N.J. AU - Meer, J.W.M. van der PY - 2009 UR - https://hdl.handle.net/2066/80503 AB - Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of recurrence was estimated in 130 deficient patients, with separate estimates for those with each of protein S, protein C, and antithrombin deficiency, and in eight non-deficient patients with prior venous thromboembolism. All patients were also tested for factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX and XI, and hyperhomocysteinemia. There were 81 recurrent events among 130 deficient patients. Median follow-up was 4.6 years. Annual incidences (95% confidence interval) of recurrent venous thromboembolism were 8.4% (5.8-11.7) for protein S deficiency, 6.0% (3.9-8.7) for protein C deficiency, 10.0% (6.1-15.4) for antithrombin deficiency, and overall 7.7% (6.1-9.5). Relative risk of recurrence in patients with a spontaneous versus provoked first event was 1.5 (0.95-2.3). Cumulative recurrence rates at 1, 5 and 10 years were 15%, 38% and 53%. Relative risk of recurrence with concomitant defects was 1.4 (0.7-2.6) (1 defect) and 1.4 (0.8-2.7) (> or =2 defects). Annual incidence was 1.0% (0.03-5.5) in eight non-deficient patients. Annual incidence of major bleeding in deficient patients on oral anticoagulant treatment was 0.5% (0.2-1.0). We conclude that patients with a hereditary protein S, protein C or antithrombin deficiency appear to have a high absolute risk of recurrence. This risk is increased after a first spontaneous event, and by concomitance of other thrombophilic defects. TI - High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. EP - 99 SN - 0340-6245 IS - iss. 1 SP - 93 JF - Thrombosis and Haemostasis VL - vol. 101 DO - https://doi.org/10.1160/TH08-06-0364 ER - TY - JOUR AU - Vis, J.C. AU - Engelen, K. van AU - Timmermans, J. AU - Hamel, B.C.J. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/79872 AB - Down syndrome is the most common chromosomal abnormality. A simultaneous occurrence with Marfan syndrome is extremely rare. We present a case of a 28-year-old female with Down syndrome and a mutation in the fibrillin-1 gene. The patient showed strikingly few manifestations of Marfan syndrome. Although variable expression is known to be present in Marfan syndrome, phenotypic expression of Marfan syndrome in our patient might be masked by the co-occurrence of Down syndrome. (Neth Heart J 2009;17:345-8.). TI - Marfan syndrome masked by Down syndrome? EP - 348 SN - 1568-5888 IS - iss. 9 SP - 345 JF - Netherlands Heart Journal VL - vol. 17 ER - TY - JOUR AU - Vis, J.C. AU - Timmermans, J. AU - Post, M.C. AU - Budts, W. AU - Schepens, M.A. AU - Thijs, V. AU - Schonewille, W.J. AU - Bie, R.M. de AU - Plokker, H.W.M. AU - Tijssen, J.G.P. AU - Mulder, B.J. PY - 2009 UR - https://hdl.handle.net/2066/80231 AB - OBJECTIVE: A high prevalence of migraine has been described in various forms of congenital heart disease, with and without shunt. In this study we investigated the prevalence of migraine in patients with Marfan syndrome (MFS). METHODS: All 457 adult patients with MFS from the participating centres and 194 controls received a validated questionnaire about headache. Migraine was diagnosed according to the International Headache Society criteria, by three independent neurologists, blinded to patient files. RESULTS: Response rate was 68% and 56% in Marfan patients and controls, respectively. Forty percent of the 309 responding MFS patients (mean age 40+/-14 years; 51% females) and 28% of the 102 controls (mean age 43+/-15 years; 58% females), suffered from migraine (p=0.03). The prevalence of migraine with aura (MA) was 22% in MFS patients and 14% in controls (p=0.06). We found MFS to be an independent risk factor for having overall migraine (OR 1.7; 95%CI 1.1-2.8), also after adjustment for age and gender (OR 1.9; 95%CI 1.1-3.1; p=0.02) and for MA after adjustment for gender (OR 2.0; 95%CI 1.1-3.7; p=0.04). In patient with MFS, previous aortic root surgery appeared to be an independent risk factor for having MA (OR 2.2; 95%CI; 1.2.-4.0, p=0.01) adjusted for gender. CONCLUSION: MFS is an independent risk factor for having overall migraine and MA. Moreover, we found that a history of aortic root surgery seems to be associated with an increased risk of MA. TI - Increased prevalence of migraine in Marfan syndrome. EP - 334 SN - 0167-5273 IS - iss. 3 SP - 330 JF - International Journal of Cardiology VL - vol. 136 DO - https://doi.org/10.1016/j.ijcard.2008.05.037 ER - TY - JOUR AU - Kievit, P.C. AU - Brouwer, M.A. AU - Veen, G. AU - Aengevaeren, W.R.M. AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/81178 AB - BACKGROUND: In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. METHODS: In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery <48 h after fibrinolysis received randomized antithrombotic treatment until 3-month follow-up angiography. Five-year clinical follow-up was complete. RESULTS: Current smokers (317 patients, 64%) had favorable clinical (age 54 vs. 60 years, P < 0.01) and angiographic (single vessel disease 61% vs. 49%, P = 0.02) baseline characteristics. Reocclusion rates were 21% (67/317) in smokers versus 32% (59/182) in non-smokers (P < 0.01). Five-year infarct-free cardiac survival did not differ: 82% vs. 85%. Reocclusion (HR 2.41, 95%CI 1.05-5.56, P = 0.04) independently predicted cardiac mortality. Smoking was independently associated with a reduced risk of reocclusion (OR 0.58, 95%CI 0.37-0.91, P = 0.02), but not with improved 5-year cardiac outcome (HR 1.34, 95%CI 0.79-2.25, P = ns). CONCLUSIONS: After successful fibrinolysis, smoking is independently associated with a more than 40% reduced risk of reocclusion, which is an independent predictor of adverse outcome. However, even with more favorable baseline characteristics smokers did not have improved 5-year cardiac outcome in this low-risk population. TI - The smoker's paradox after successful fibrinolysis: reduced risk of reocclusion but no improved long-term cardiac outcome. EP - 393 SN - 0929-5305 IS - iss. 4 SP - 385 JF - Journal of Thrombosis and Thrombolysis VL - vol. 27 DO - https://doi.org/10.1007/s11239-008-0238-6 ER - TY - JOUR AU - Lijfering, W.M. AU - Brouwer, J.L.P. AU - Veeger, N.J. AU - Bank, I. AU - Coppens, M. AU - Middeldorp, S. AU - Hamulyak, K. AU - Prins, M.H. AU - Buller, H.R. AU - Meer, J.W.M. van der PY - 2009 UR - https://hdl.handle.net/2066/81593 AB - Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis. TI - Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. EP - 5322 SN - 0006-4971 IS - iss. 21 SP - 5314 JF - Blood VL - vol. 113 DO - https://doi.org/10.1182/blood-2008-10-184879 ER - TY - JOUR AU - Werkum, J.W. van AU - Heestermans, A.A. AU - Zomer, A.C. AU - Kelder, J.C. AU - Suttorp, M.J. AU - Rensing, B.J. AU - Koolen, J.J. AU - Brueren, B.R. AU - Dambrink, J.H. AU - Hautvast, R.W. AU - Verheugt, F.W.A. AU - Berg, J.M. ten PY - 2009 UR - https://hdl.handle.net/2066/81893 AB - OBJECTIVES: This study sought to comprehensively identify predictors of stent thrombosis (ST). BACKGROUND: Given the devastating consequences of ST, efforts should be directed toward risk stratification to identify patients at highest risk for ST. METHODS: Consecutive patients with angiographic ST were enrolled. Patients who did not suffer from a ST were randomly selected in a 2:1 ratio and were matched for: 1) percutaneous coronary intervention (PCI) indication; 2) same date of index PCI; and 3) same interventional center. RESULTS: Of 21,009 patients treated with either a bare-metal or drug-eluting stent, 437 patients (2.1%) presented with a definite ST. A total of 140 STs were acute, 180 were subacute, 58 were late, and 59 were very late. Undersizing of the coronary stent, Thrombolysis In Myocardial Infarction flow grade <3, present malignancy, presence of intermediate coronary artery disease proximal and distal to the culprit lesion, dissection, lack of aspirin, bifurcation lesions, ejection fraction <30%, and younger age were associated with ST. The lack of clopidogrel therapy at the time of ST in the first 30 days after the index PCI (hazard ratio [HR]: 36.5, 95% confidence interval [CI]: 8.0 to 167.8), between 30 days and 6 months after the index PCI (HR: 4.6, 95% CI: 1.4 to 15.3), and beyond 6 months (HR: 5.9, 95% CI: 1.7 to 19.8) after the index PCI was strongly associated with ST. CONCLUSIONS: Important correlates of ST were identified. Discontinuation of clopidogrel, undersizing of the coronary stent, present malignancy, and intermediate (>or=50% to <70% stenosis) coronary artery disease proximal to the culprit lesion were the strongest predictors of ST. TI - Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry. EP - 1409 SN - 0735-1097 IS - iss. 16 SP - 1399 JF - Journal of the American College of Cardiology VL - vol. 53 DO - https://doi.org/10.1016/j.jacc.2008.12.055 ER - TY - JOUR AU - Elsenberg, E.H. AU - Werkum, J.W. van AU - Wal, R.M. van de AU - Zomer, A.C. AU - Bouman, H.J. AU - Verheugt, F.W.A. AU - Berg, J.M. ten AU - Hackeng, C.M. PY - 2009 UR - https://hdl.handle.net/2066/81247 AB - High on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) are independently associated with an increased risk of atherothrombotic events. However, despite this positive correlation, the definitions of both HCPR and HAPR vary largely throughout studies and between different platelet function assays. The aim of the present study was to explore clinical and laboratory parameters that are associated with HCPR and HAPR as measured with different platelet function tests. 530 clopidogrel and aspirin pre-treated patients undergoing elective PCI (percutaneous coronary intervention) were enrolled. Platelet function measurements were performed with: optical aggregometry, the VerifyNow device and PFA-100 cartridges (including the novel INNOVANCE P2Y assay). HCPR as measured with Adenosin-Di-Phospate-induced (ADP) aggregation based tests was associated with clinical factors such as older age, female gender and Diabetes mellitus (DM). The VerifyNow P2Y12 assay was significantly influenced by haemoglobin and haematocrit levels. HAPR as measured with aggregation based tests was significantly influenced by the presence of malignancy, BMI (Body-Mass Index), older age and increased levels of hsCRP (high sensitivity c-reactive proteine). The PFA-100 COL/EPI (collagen-epinephrine) and COL/ADP (collagen-ADP) cartridges were significantly influenced by monocyte count, hs-CRP, MPV (mean platelet volume), vWF-antigen (von Willebrand factor) and vWF-activity. HCPR as measured with the novel INNOVANCE P2Y cartridge was associated with clinical determinants such as BMI, female gender, impaired LVEF (left ventricular ejection fraction), renal failure and dosing of clopidogrel. Laboratory markers that were associated with HCPR as measured with INNOVANCE P2Y were platelet count, white blood cells (WBC), hsCRP and fibrinogen. Both HCPR and HAPR are highly dependent on the type of platelet function assay. Each platelet function assay, in turn, is significantly influenced by distinct clinical and laboratory variables. TI - The influence of clinical characteristics, laboratory and inflammatory markers on 'high on-treatment platelet reactivity' as measured with different platelet function tests. EP - 727 SN - 0340-6245 IS - iss. 4 SP - 719 JF - Thrombosis and Haemostasis VL - vol. 102 DO - https://doi.org/10.1160/TH09-05-0285 ER - TY - JOUR AU - Werkum, J.W. van AU - Heestermans, A.A. AU - Korte, F.I. de AU - Kelder, J.C. AU - Suttorp, M.J. AU - Rensing, B.J. AU - Zwart, B. de AU - Brueren, B.R. AU - Koolen, J.J. AU - Dambrink, J.H. AU - Hof, A.W. van 't AU - Verheugt, F.W.A. AU - Berg, J.M. ten PY - 2009 UR - https://hdl.handle.net/2066/79950 AB - BACKGROUND: There are limited data on the long-term clinical outcome after an angiographically confirmed (definite) stent thrombosis (ST). METHODS AND RESULTS: Four hundred thirty-one consecutive patients with a definite ST were enrolled in this multicenter registry. The primary end point was the composite of cardiac death and definite recurrent ST. Secondary end points were all-cause death, cardiac death, definite recurrent ST, definite and probable recurrent ST, any myocardial infarction, and any target-vessel revascularization. The primary end point occurred in 111 patients after a median follow-up of 27.1 months. The estimated cumulative event rates at 30 days and 1, 2, and 3 years were 18.0%, 23.6%, 25.2%, and 27.9%, respectively. The cumulative incidence rates of definite recurrent ST, definite or probable recurrent ST, any myocardial infarction, and any target-vessel revascularization were 18.8%, 20.1%, 21.3%, and 32.0%, respectively, at the longest available follow-up. Independent predictors for the primary end point were diabetes mellitus, total stent length, severe calcification, American College of Cardiology/American Heart Association B2-C lesions, TIMI (Thrombolysis In Myocardial Infarction) flow grade <3 after percutaneous coronary intervention, and left ventricular ejection fraction <45%. The implantation of an additional coronary stent during the first ST was also associated with unfavorable outcome. Clinical outcome was not affected by the type of previously implanted stent (drug-eluting or bare-metal stent) or the category of ST (early versus late). CONCLUSIONS: The long-term clinical outcome after a first definite ST is unfavorable, with a high mortality and recurrence rate. Diabetes mellitus, left ventricular ejection fraction <45%, long total stent length, complex coronary lesions, TIMI flow grade <3 after percutaneous coronary intervention, and implantation of an additional coronary stent during the emergent percutaneous coronary intervention for the ST were associated with this unfavorable outcome. TI - Long-term clinical outcome after a first angiographically confirmed coronary stent thrombosis: an analysis of 431 cases. EP - 834 SN - 0009-7322 IS - iss. 6 SP - 828 JF - Circulation VL - vol. 119 DO - https://doi.org/10.1161/CIRCULATIONAHA.108.799403 ER - TY - JOUR AU - Schiks, I.E.J.M. AU - Schoonhoven, L. AU - Aengevaeren, W.R.M. AU - Nogarede-Hoekstra, C. AU - Achterberg, T. van AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/79970 AB - AIM AND OBJECTIVES: To investigate if ambulation four hours after sheath removal can replace ambulation 10 hours or more after sheath removal with regard to puncture site complications after percutaneous coronary interventions and to examine patient comfort in both groups. BACKGROUND: Early ambulation after percutaneous coronary intervention may facilitate earlier hospital discharge. Whether this approach is safe, is unknown. DESIGN: A non-randomised comparative study. METHODS: Percutaneous coronary intervention was performed by femoral approach. Registered nurses of the ward removed the sheath and haemostasis was achieved by manual compression. After bed rest with a compression bandage for four hours, the patients in the early ambulation group were ambulated. The patients in the control group stayed in bed till the next morning. Primary study endpoint was the composition of puncture site complications: haematoma, bleeding, false aneurysm and arteriovenous fistula. Secondary endpoints were occurrence of vasovagal collapse after mobilisation, back pain and problems with voiding. RESULTS: In the early ambulation group (n = 329) the total number of complications was nine (2.7%), vs. six (3.0%) in the control group (n = 202). The complication rate in the early ambulation group is not increased compared to the control group (test for non-inferiority p = 0.002). Hence non-inferiority is accepted and practical equivalence shown. There were no statistically significant differences concerning patient comfort between the groups. CONCLUSIONS: Early ambulation four hours after femoral sheath removal is feasible and safe. The incidence of puncture site complications in the early ambulation group is not increased in comparison with the group with prolonged bed rest. RELEVANCE TO CLINICAL PRACTICE: Patients could possibly be discharged earlier after percutaneous coronary intervention, allowing percutaneous coronary intervention in an ambulant setting. Further research should confirm these findings and extend the research to the effect of various closure devices in early ambulation and on patients' well-being. TI - Ambulation after femoral sheath removal in percutaneous coronary intervention: a prospective comparison of early vs. late ambulation. EP - 1870 SN - 0962-1067 IS - iss. 13 SP - 1862 JF - Journal of Clinical Nursing VL - vol. 18 DO - https://doi.org/10.1111/j.1365-2702.2008.02587.x ER - TY - JOUR AU - Meijer, P. AU - Oyen, W.J.G. AU - Dekker, D. AU - Broek, P.H.H. van den AU - Wouters, C.W. AU - Boerman, O.C. AU - Scheffer, G.J. AU - Smits, P. AU - Rongen, G.A.P.J.M. PY - 2009 UR - https://hdl.handle.net/2066/81647 AB - OBJECTIVE: Statins may increase extracellular adenosine formation from adenosine monophosphate by enhancing ecto-5'-nucleotidase activity. This theory was tested in humans using dipyridamole-induced vasodilation as a read-out for local adenosine formation. Dipyridamole inhibits the transport of extracellular adenosine into the cytosol resulting in increased extracellular adenosine and subsequent vasodilation. In addition, we studied the effect of statin therapy in a forearm model of ischemia-reperfusion injury. METHODS AND RESULTS: Volunteers randomly received rosuvastatin or placebo in a double-blind parallel design (n=21). The forearm vasodilator response to intraarterial dipyridamole was determined in the absence and presence of the adenosine antagonist caffeine. During a separate visit the vasodilator response to nitroprusside and adenosine was established. In addition, healthy men were randomly divided in 3 groups to receive either placebo (n=10), rosuvastatin (n=22), or rosuvastatin combined with intravenous caffeine (n=12). Subsequently, volunteers performed forearm ischemic exercise. At reperfusion, Tc-99m-labeled annexin A5 was infused intravenously and scintigraphic images were acquired, providing an early marker of cell injury. Rosuvastatin treatment significantly increased the vasodilator response to dipyridamole, which was prevented by caffeine. Rosuvastatin did not influence the response to either sodium nitroprusside or adenosine indicating a specific interaction between rosuvastatin and dipyridamole, which does not result from an effect of rosuvastatin on adenosine clearance nor adenosine-receptor affinity or efficacy. Rosuvastatin increased tolerance to ischemia-reperfusion injury, which was attenuated by caffeine. CONCLUSIONS: Rosuvastatin increases extracellular adenosine formation, which provides protection against ischemia-reperfusion injury in humans in vivo. Therefore, statins and dipyridamole may interact synergistically. TI - Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection. EP - 968 SN - 1079-5642 IS - iss. 6 SP - 963 JF - Arteriosclerosis, Thrombosis, and Vascular Biology VL - vol. 29 DO - https://doi.org/10.1161/ATVBAHA.108.179622 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/81647/81647.pdf?sequence=1 ER - TY - JOUR AU - Luesink, M. AU - Smeets, J.L.R.M. AU - Brons, P.P.T. AU - Kapusta, L. PY - 2009 UR - https://hdl.handle.net/2066/80026 AB - An 8-year-old girl who was recently diagnosed as having anaplastic large-cell lymphoma presented with atrial tachycardia and dilated cardiomyopathy, which is a contraindication for further treatment with cardio-toxic chemotherapy. After starting digoxin therapy, the dilated cardiomyopathy resolved. Repeated episodes of atrial tachycardia in this case were not caused by any common disorder but were due to mechanical stimulation by a central venous catheter. Central venous catheters are known to cause mainly ventricular arrhythmias. However, atrial tachycardia is a rare manifestation of arrhythmia due to mechanical stimulation of the heart by a central venous catheter, with potentially important cardiovascular consequences. TI - An unusual cause of atrial tachycardia in a young patient with lymphoma. EP - 450 SN - 0009-9228 IS - iss. 4 SP - 449 JF - Clinical Pediatrics VL - vol. 48 DO - https://doi.org/10.1177/0009922808323119 ER - TY - JOUR AU - Mavinkurve-Groothuis, A.M.C. AU - Groot-Loonen, J.J. AU - Bellersen, L. AU - Pourier, M.S. AU - Feuth, A.B. AU - Bokkerink, J.P.M. AU - Hoogerbrugge, P.M. AU - Kapusta, L. PY - 2009 UR - https://hdl.handle.net/2066/79606 AB - BACKGROUND: Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of survivors of childhood malignancies. The aims of this study were to document plasma concentrations of cardiac troponin T (cTnT) and NT-pro-brain natriuretic peptide (NT-pro-BNP) in a large group of asymptomatic long-term survivors of childhood cancer treated with anthracyclines, and to study the relation of the abnormal biomarker levels with different risk factors for anthracycline-induced cardiotoxicity and conventional echocardiographic parameters. PROCEDURES: One hundred twenty-two asymptomatic survivors of childhood cancer underwent a detailed echocardiography. Blood samples were taken to determine the levels of NT-pro-BNP and cTnT. RESULTS: None of the survivors had abnormal cTnT levels. Thirteen percent of the survivors (n = 16) had abnormal NT-pro-BNP levels. Abnormal NT-pro-BNP levels were significantly related to cumulative anthracycline dosage (P < 0.003). Eleven of 31 survivors (35%) treated with cumulative anthracycline dose of 300 mg/m(2) or more, had abnormal NT-pro-BNP levels which were significantly related to end-diastolic left ventricular internal diameter (LVIDd) indexed for body surface area (BSA) (P < 0.01). CONCLUSION: Cardiac TnT does not contribute to the early detection of late onset anthracycline-induced cardiotoxicity. Abnormal levels of NT-pro-BNP were detected in 13% of 122 asymptomatic, long-term survivors of childhood cancer. Follow-up of these survivors is essential to answer the question whether NT-pro-BNP is an early marker for late onset anthracycline-induced cardiotoxicity. TI - Abnormal NT-pro-BNP levels in asymptomatic long-term survivors of childhood cancer treated with anthracyclines. EP - 636 SN - 1545-5009 IS - iss. 5 SP - 631 JF - Pediatric Blood & Cancer VL - vol. 52 DO - https://doi.org/10.1002/pbc.21913 ER - TY - JOUR AU - Voermans, N.C. AU - Timmermans, J. AU - Alfen, N. van AU - Pillen, S. AU - Akker, J.W. op den AU - Lammens, M.M.Y. AU - Zwarts, M.J. AU - Rooij, I.A.L.M. van AU - Hamel, B.C.J. AU - Engelen, B.G.M. van PY - 2009 UR - https://hdl.handle.net/2066/81084 AB - Marfan syndrome is a clinically and allelic heterogeneous, heritable connective tissue disorder with infrequently reported neuromuscular features. This study is the first to delineate these symptoms in a non-selected population. Neuromuscular involvement was evaluated in 10 Marfan patients through a standardized questionnaire, physical examination, nerve conduction study (NCS), needle electromyography (EMG), muscle ultrasound, laboratory investigation, and muscle biopsy. Existing neuroimages were screened for dural ectasia and spinal meningeal cysts. Twenty healthy controls with similar age distribution completed the questionnaire. The results showed that various neuromuscular symptoms occur more frequently in the patients. Four older patients reported muscle weakness, five patients had a mild-to-moderate reduction in vibration sense, and all older patients mentioned mild functional impairments. NCS showed axonal polyneuropathy in four and EMG myopathic and neurogenic changes in all patients. Increased echo intensity and atrophy on muscle ultrasound was found in more than half of the patients. Muscle biopsies obtained in two patients showed myopathic changes in the older, female patient. In conclusion, the majority of Marfan patients exhibited neuromuscular symptoms characterized as myopathy or polyneuropathy or both, and signs of lumbosacral radiculopathy, with symptoms being most pronounced in the older patients. Although meriting corroboration, these findings indicate a need to further the awareness of neuromuscular involvement in this population. TI - Neuromuscular features in Marfan syndrome. EP - 37 SN - 0009-9163 IS - iss. 1 SP - 25 JF - Clinical Genetics VL - vol. 76 DO - https://doi.org/10.1111/j.1399-0004.2009.01197.x ER - TY - JOUR AU - Evertz, R. AU - Bennekom, S. van AU - Dirksen, M.T. AU - Verheugt, F.W.A. PY - 2009 UR - https://hdl.handle.net/2066/80464 TI - Hotline sessions of the 31st European Congress of Cardiology. EP - 2565 SN - 0195-668X IS - iss. 21 SP - 2562 JF - European Heart Journal VL - vol. 30 ER - TY - JOUR AU - Robbers-Visser, D. AU - Kapusta, L. AU - Osch-Gevers, L. van AU - Strengers, J.L. AU - Boersma, E. AU - Rijke, Y.B. de AU - Boomsma, F. AU - Bogers, A.J. AU - Helbing, W.A. PY - 2009 UR - https://hdl.handle.net/2066/79616 AB - OBJECTIVE: This study assessed clinical condition at midterm follow-up after total cavopulmonary connection for a functionally univentricular heart performed on children younger than 5 years. METHODS: Thirty-four Fontan patients (median age 10.4 years, range 6.8-20.7 years, 22 boys, median follow-up 7.8 years, 5.0-17.8 years) underwent electrocardiography, Holter monitoring, bicycle exercise testing, cardiac magnetic resonance imaging, and N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) analysis. RESULTS: Twenty-three patients (68%) were in sinus rhythm. Holter monitoring demonstrated normal mean heart rate, low maximal heart rate, and no clinically significant arrhythmias or sinus node dysfunction. With maximal bicycle ergometry (n = 19), maximum workload (60% of normal), maximum heart rate (90% of normal), and maximal oxygen uptake (69% of normal) were all significantly lower in the Fontan group than in a control group (P < .001). Variables of submaximal exercise indicated less efficient oxygen uptake during exercise in all Fontan patients. Ejection fraction was lower than in control subjects (59% +/- 13% vs 69% +/- 5%, P < .001). Mean end-diastolic and end-systolic volumes and ventricular mass were higher than in control subjects (P < .001). Mean NT-pro-BNP levels were increased relative to reference values, but only 8 patients had levels above the upper reference limit. CONCLUSION: At midterm follow-up, Fontan patients were in acceptable clinical condition, with preserved global ventricular function, moderately decreased exercise capacity, and NT-pro-BNP levels within reference range. Systemic ventricular mass was elevated, however, suggesting contractility-afterload mismatch. Long-term consequences for ventricular function merit further investigation. TI - Clinical outcome 5 to 18 years after the Fontan operation performed on children younger than 5 years. EP - 95 SN - 0022-5223 IS - iss. 1 SP - 89 JF - Journal of Thoracic and Cardiovascular Surgery VL - vol. 138 DO - https://doi.org/10.1016/j.jtcvs.2008.12.027 ER - TY - JOUR AU - Windhausen, F. AU - Hirsch, A. AU - Fischer, J. AU - Zee, P.M. van der AU - Sanders, G.T. AU - Straalen, J.P. van AU - Cornel, J.H. AU - Tijssen, J.G.P. AU - Verheugt, F.W.A. AU - Winter, R.J. de PY - 2009 UR - https://hdl.handle.net/2066/79513 AB - BACKGROUND: We assessed the value of cystatin C for improvement of risk stratification in patients with non-ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective invasive treatment strategy (SIS) with regard to renal function. METHODS: Patients (n = 1128) randomized to an EIS or an SIS in the ICTUS trial were stratified according to the tertiles of the cystatin C concentration at baseline. The end points were death within 4 years and spontaneous myocardial infarction (MI) within 3 years. RESULTS: Mortality was 3.4%, 6.2%, and 13.5% in the first, second, and third tertiles, respectively, of cystatin C concentration (log-rank P < 0.001), and the respective rates of spontaneous MI were 5.5%, 7.5%, and 9.8% (log-rank P = 0.03). In a multivariate Cox regression analysis, the cystatin C concentration in the third quartile remained independently predictive of mortality [hazard ratio (HR), 2.04; 95% CI, 1.02-4.10; P = 0.04] and spontaneous MI (HR, 1.95; 95% CI, 1.05-3.63; P = 0.04). The mortality rate in the second tertile was lower with the EIS than with the SIS (3.8% vs 8.7%). In the third tertile, the mortality rates with the EIS and the SIS were, respectively, 15.0% and 12.2% (P for interaction = 0.04). Rates of spontaneous MI were similar for the EIS and the SIS within cystatin C tertiles (P for interaction = 0.22). CONCLUSIONS: In patients with nSTE-ACS and an increased cTnT concentration, mild to moderate renal dysfunction is associated with a higher risk of death and spontaneous MI. Use of cystatin C as a serum marker of renal function may improve risk stratification. TI - Cystatin C for enhancement of risk stratification in non-ST elevation acute coronary syndrome patients with an increased troponin T. EP - 1125 SN - 0009-9147 IS - iss. 6 SP - 1118 JF - Clinical Chemistry VL - vol. 55 DO - https://doi.org/10.1373/clinchem.2008.119669 ER - TY - JOUR AU - Hirsch, A. AU - Windhausen, F. AU - Tijssen, J.G.P. AU - Oude Ophuis, A.J.M. AU - Giessen, W.J. van der AU - Zee, P.M. van der AU - Cornel, J.H. AU - Verheugt, F.W.A. AU - Winter, R.J. de PY - 2009 UR - https://hdl.handle.net/2066/80830 AB - AIMS: In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. METHODS AND RESULTS: The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI. CONCLUSION: The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies. TI - Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias. EP - 654 SN - 0195-668X IS - iss. 6 SP - 645 JF - European Heart Journal VL - vol. 30 ER - TY - JOUR AU - Yap, S.C. AU - Drenthen, W. AU - Meijboom, F.J. AU - Moons, P. AU - Mulder, B.J. AU - Vliegen, H.W. AU - Dijk, A.P.J. van AU - Jaddoe, V.W. AU - Steegers, E.A.P. AU - Roos-Hesselink, J.W. AU - Pieper, P.G. PY - 2009 UR - https://hdl.handle.net/2066/81862 AB - OBJECTIVE: To compare the risks of complications during pregnancy in women with repaired and unrepaired atrial septal defects (ASDs) without associated complex cardiac lesions. DESIGN: A retrospective multicentre study. SETTING: Tertiary centres in the Netherlands and Belgium. POPULATION: Women with ASD without associated complex cardiac lesions. METHODS: Women were identified using two congenital heart disease registries. One hundred women were identified who had 243 pregnancies, including 49 miscarriages and six terminations of pregnancy. Detailed information on each completed pregnancy (n = 188; unrepaired ASD, n = 133; repaired ASD, n = 55) was obtained using medical records and telephone interviews. In addition, data from the Generation R database (a prospective cohort study; n = 9667) were used to determine the background risk (control group). MAIN OUTCOME MEASURES: Adjusted odds ratios (AORs) for cardiac, obstetric and neonatal events controlled for multiple pregnancies per woman using general estimating equation analysis. RESULTS: Women with an unrepaired ASD had a higher risk of neonatal events (AOR = 2.99, 95% confidence interval [CI] 1.14-7.89, P = 0.027) than women with a repaired ASD. The risk of cardiac and obstetric complications was comparable between women with unrepaired and repaired ASDs. Compared with the general population, women with an unrepaired ASD had higher risks of pre-eclampsia (AOR = 3.54, 95% CI 1.26-9.98, P = 0.017), small-for-gestational-age births (AOR = 1.95, 95% CI 1.15-3.30, P = 0.013) and fetal mortality (AOR = 5.55, 95% CI 1.77-17.4, P = 0.003). By contrast, no differences were observed when comparing women with a repaired ASD versus controls. CONCLUSIONS: Women with an unrepaired ASD are at increased risk of neonatal events in comparison with women with a repaired ASD. Compared with the general population, women with an unrepaired ASD are at increased risk of pre-eclampsia, small-for-gestational-age births and fetal mortality. TI - Comparison of pregnancy outcomes in women with repaired versus unrepaired atrial septal defect. EP - 1601 SN - 1470-0328 IS - iss. 12 SP - 1593 JF - Bjog : an International Journal of Obstetrics and Gynaecology VL - vol. 116 DO - https://doi.org/10.1111/j.1471-0528.2009.02301.x ER -