Showing papers by "Isabelle C. Van Gelder published in 2006"
TL;DR: In this paper, mutations in the plakophilin-2 gene (PKP2) were found in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC).
Abstract: Background— Mutations in the plakophilin-2 gene (PKP2) have been found in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC). Hence, genetic screening can potentially be a valuable tool in the diagnostic workup of patients with ARVC. Methods and Results— To establish the prevalence and character of PKP2 mutations and to study potential differences in the associated phenotype, we evaluated 96 index patients, including 56 who fulfilled the published task force criteria. In addition, 114 family members from 34 of these 56 ARVC index patients were phenotyped. In 24 of these 56 ARVC patients (43%), 14 different (11 novel) PKP2 mutations were identified. Four different mutations were found more than once; haplotype analyses revealed identical haplotypes in the different mutation carriers, suggesting founder mutations. No specific genotype-phenotype correlations could be identified, except that negative T waves in V2 and V3 occurred more often in PKP2 mutation carriers (P<0.05). Of th...
311 citations
TL;DR: HSP induction protects against atrial tachycardia–induced remodeling, the protective effect in HL-1 myocytes requires HSP27 induction and phosphorylation, and the orally administered HSP inducer GGA protects against AF in a clinically relevant animal model.
Abstract: There is evidence suggesting that heat shock proteins (HSPs) may protect against clinical atrial fibrillation (AF). We evaluated the effect of HSP induction in an in vitro atrial cell line (HL-1) model of tachycardia remodeling and in tachypaced isolated canine atrial cardiomyocytes. We also evaluated the effect of HSP induction on in vivo AF promotion by atrial tachycardia-induced remodeling in dogs. Tachypacing (3 Hz) significantly and progressively reduced Ca(2+) transients and cell shortening of HL-1 myocytes over 4 hours. These reductions were prevented by HSP-inducing pretreatments: mild heat shock, geranylgeranylacetone (GGA), and transfection with human HSP27 or the phosphorylation-mimicking HSP27-DDD. However, treatment with HSP70 or the phosphorylation-deficient mutant HSP27-AAA failed to alter tachycardia-induced Ca(2+) transient and cell-shortening reductions, and downregulation (short interfering RNA) of HSP27 prevented GGA-mediated protection. Tachypacing (3 Hz) for 24 hours in vitro significantly reduced L-type Ca(2+) current and action potential duration in canine atrial cardiomyocytes; these effects were prevented when tachypacing was performed in cells exposed to GGA. In vivo treatment with GGA increased HSP expression and suppressed refractoriness abbreviation and AF promotion in dogs subjected to 1-week atrial tachycardia-induced remodeling. In conclusion, our findings indicate that (1) HSP induction protects against atrial tachycardia-induced remodeling, (2) the protective effect in HL-1 myocytes requires HSP27 induction and phosphorylation, and (3) the orally administered HSP inducer GGA protects against AF in a clinically relevant animal model. These findings advance our understanding of the biochemical determinants of AF and suggest the possibility that HSP induction may be an interesting novel approach to preventing clinical AF.
164 citations
TL;DR: Stringency of the approach to rate control, based on the comparison of the AFFIRM and RACE studies, was not associated with an important difference in clinical events.
Abstract: Aims The AFFIRM and RACE studies showed that rate control is an acceptable treatment strategy for atrial fibrillation (AF). We examined whether strict rate control offers benefit over more lenient rate control. Methods and Results We compared the outcome of patients enrolled in the rate-control arms of AFFIRM and RACE, using data from patients who met a composite of overlapping inclusion and exclusion criteria. We evaluated 1091 patients, 874 from AFFIRM and 217 from RACE. In AFFIRM, the rate-control strategy aimed for a resting heart rate � 80 bpm and heart rate during daily activity of � 110 bpm. In RACE, a more lenient approach was taken: resting heart rate ,100 bpm. Primary endpoint was a composite of mortality, cardiovascular hospitalization, and myocardial infarction. Mean heart rate across all follow-up visits for patients in AF was lower in AFFIRM (76.1 vs. 83.4 bpm). Event-free survival for the occurrence of the primary endpoint did not differ (64% in AFFIRM vs. 66% in RACE). Patients with mean heart rates during AF within the AFFIRM (� 80) or RACE (,100) criteria had a better outcome than patients with heart rates � 100 (hazard ratios 0.69 and 0.58, respectively, for � 80 and ,100 compared with � 100 bpm). Conclusion Stringency of the approach to rate control, based on the comparison of the AFFIRM and RACE studies, was not associated with an important difference in clinical events.
138 citations
TL;DR: Data demonstrate that upregulation of Hsp, especially Hsp27, protects tachy-paced atrial myocytes from myolysis and may represent a novel therapeutic approach in AF.
118 citations
TL;DR: AssERT is a multicenter, cohort follow-up, and single-blinded randomized trial in elderly hypertensive patients with a pacemaker recently implanted for sinus or atrioventricular node disease evaluating the hypothesis that among pacemaker patients without a previous history of AF, detection of AHRE predicts an increased risk of stroke and systemic embolism.
113 citations
TL;DR: In patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs.
74 citations
TL;DR: AZD7009 exhibited dose-dependent effects in converting AF to SR in AF patients and appeared to be associated with a low risk of proarrhythmia despite continued administration during a period of heightened vulnerability.
62 citations
TL;DR: The results of these trials suggest that whereas the two strategies may be equivalent for some patient populations, with both approaches requiring accompanying anticoagulation therapy, the restoration and maintenance of sinus rhythm provide important haemodynamic as well as subjective benefits not afforded by rate control.
Abstract: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting young as well as elderly patients and presenting a major therapeutic challenge for clinical cardiologists. Recent research has elucidated the progressive nature of AF, including the structural and electrical remodelling that may become manifest if normal sinus rhythm is not restored, and the serious morbidities associated with long-term disease. The controversy over the merits of ventricular rate control vs. the restoration and maintenance of normal sinus rhythm in the treatment of AF has been explored in a number of large-scale, randomized clinical trials. The results of these trials suggest that whereas the two strategies may be equivalent for some patient populations, with both approaches requiring accompanying anticoagulation therapy, the restoration and maintenance of sinus rhythm provide important haemodynamic as well as subjective benefits not afforded by rate control. Although early intervention to limit the progression of this arrhythmia is hindered by the limitations of existing anti-arrhythmic therapies, it is nevertheless a critical goal.
60 citations
TL;DR: In advanced CHF patients, AF affects (NT-)ANP levels, but not (NT-pro)BNP levels; NT-proBNP is an independent determinant of prognosis in advancedCHF, irrespective of the rhythm, AF, or sinus rhythm.
Abstract: Aims To study the determinants of natriuretic peptides in advanced chronic heart failure (CHF) patients with and without atrial fibrillation (AF) and to evaluate the prognostic value of natriuretic peptides in AF compared with sinus rhythm patients with advanced CHF, Methods and results The study group comprised 354 advanced CHIF patients (all New York Heart Association (NYHA) III/IV], including 76 AF patients. AF patients were older (70 +/- 7 vs. 67 +/- 8; P = 0.01), and non-ischaemic CHF was more common (42 vs. 19%; P = 0.002) than in sinus rhythm patients, but left-ventricular ejection fraction was comparable (0.23 +/- 0.08 vs. 0.24 +/- 0.07; P = ns). At baseline, (NT-)ANP and NT-proBNP levels were significantly higher in AF patients, compared with those in sinus rhythm. By multivariate regression analysis, AF was identified as independent determinant of (NT-)ANP, but not of (NT-pro)BNP levels. After a mean follow-up of 3.2 +/- 0.9 (range 0.4 +/- 5.4) years, cardiovascular mortality was comparable (55 vs. 47%; P = ns). In both groups, AF and sinus rhythm, NT-proBNP [AF: adjusted HR 5.8 (1.3 - 25.4), P = 0.02; sinus rhythm: adjusted HR 3.1 (1.7 - 5.7), P <0.001] was an independent risk indicator of cardiovascular mortality. Conclusion In advanced CHF patients, AF affects (NT-)ANP levels, but not (NT-pro)BNP levels. NT-proBNP is an independent determinant of prognosis in advanced CHF, irrespective of the rhythm, AF or sinus rhythm.
58 citations
TL;DR: Among patients who remained on warfarin, those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate- control strategy.
Abstract: Aims To compare outcome of AF patients with effective rhythm control with patients treated with rate control.
Methods and results Out of the 266 AF patients randomized to rhythm control in the RACE study, 49 patients turned to long-term sinus rhythm and were continuously treated with oral anticoagulation. The incidence of the primary endpoint in these patients was compared to that in 178 patients out of the initial 256 rate-control patients of RACE who were in AF and using oral anticoagulation continuously. Baseline characteristics of both groups were not different. After a mean follow-up of 2.3±0.6 years, the primary endpoint (a composite of cardiovascular mortality, heart failure, thrombo-embolic complications (TECs), bleeding, serious adverse effects of antiarrhythmic drugs and pacemaker implants) was 22.4% in the rhythm-control group vs. 15.2% in the rate-control group. Multivariable regression analysis indicated coronary artery disease, heart failure, and digitalis as independent risk indicators of cardiovascular morbidity and mortality. Chronic sinus rhythm did not matter.
Conclusion Among patients who remained on warfarin, those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate-control strategy.
54 citations
TL;DR: RV pacing was associated with an increased risk of HF in asymptomatic ICD patients, particularly in those with preexistent left ventricular dysfunction.
TL;DR: Patients with atrial fibrillation and advanced chronic heart failure with higher heart rates are comparable to those with lowerheart rates, and lower heart rates seem associated with a worse outcome.
TL;DR: Cox maze III surgery is a highly effective therapy for drug-refractory lone AF, and therefore remains an alternative to transvenous pulmonary vein ablation.
TL;DR: An acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy, and verapamil has no beneficial effect in a serial cardioversions strategy.
TL;DR: It is demonstrated that history of AF is associated with increased risk of appropriate shocks and cardiovascular mortality in primary prevention ICD patients with left ventricular dysfunction.
Abstract: AIMS: Atrial fibrillation (AF) is often present in patients with left ventricular dysfunction who receive an implantable cardioverter-defibrillator (ICD). The purpose of this study was to investigate whether AF is associated with appropriate shocks and cardiovascular mortality in primary prevention ICD patients with left ventricular dysfunction. METHODS AND RESULTS: We included 80 primary prevention ICD patients with left ventricular dysfunction and compared the outcome between patients with a history of AF (n=29) and patients with no history of AF (n=51). The primary endpoint was occurrence of appropriate shocks. Secondary endpoints were: (1) the composite of cardiovascular mortality/appropriate shocks; and (2) inappropriate shocks. During follow-up (median 8 months, range 1-60), patients with a history of AF more often received appropriate shocks than patients with no history of AF (24 vs. 6%, P=0.03). The composite endpoint of cardiovascular mortality/appropriate shocks was also more likely to occur in patients with a history of AF (34 vs. 12%, P=0.02). History of AF predicted appropriate shocks (HR 6.9, 95% CI 1.7-27.5, P=0.006) and the composite endpoint of cardiovascular mortality/appropriate shocks (adjusted HR 5.1, 95% CI 1.7-15.1, P=0.003). There were no differences in occurrence of inappropriate shocks. CONCLUSION: Our study demonstrates that history of AF is associated with increased risk of appropriate shocks and cardiovascular mortality in primary prevention ICD patients with left ventricular dysfunction.
TL;DR: In this paper, the authors evaluated the correlates of sudden cardiac and nonsudden cardiac death in patients with persistent atrial fibrillation randomized to rate or rhythm control in the RAte Control vs Electrical cardioversion (RACE) study.
Abstract: This report evaluated the correlates of sudden cardiac and nonsudden cardiac death in patients with persistent atrial fibrillation randomized to rate or rhythm control in the RAte Control vs Electrical cardioversion (RACE) study. Sudden cardiac death was observed in 16 patients, 8 patients in each group. Previous myocardial infarction resulted in a 4.9-fold increased risk of sudden death (95% confidence interval 1.8 to 13.2). The use of β blockers showed their protective nature (hazard ratio 0.2, 95% confidence interval 0.05 to 0.9). The randomized treatment strategy, heart rhythm during follow-up, use of antiarrhythmic drugs, and number of stroke risk factors were not associated with sudden cardiac death. In conclusion, the treatment of underlying disease, rather than the heart rhythm, seems essential to prevent mortality.
TL;DR: This is the first randomized controlled clinical trial to prove that overdrive pacing is effective in preventing early recurrences of AT/AF, however, shortcomings of the PMOP algorithm, such as late activation, need further improvement.
TL;DR: Right atrial overdrive pacing in combination with antiarrhythmic drugs seems an attractive treatment option in drug refractory symptomatic AF patients.
Abstract: Aims Our aim was to investigate whether right atrial overdrive pacing is effective for the prevention of atrial fibrillation (AF) in patients without bradyarrhythmias. Methods and results Patients with symptomatic paroxysmal or persistent AF refractory to at least two Class I or III antiarrhythmic drugs and without bradyarrhythmias were included. Successful therapy was defined as the combination of (a) a reduction of AF burden with or without AAD use .75%, (b) total AF burden � 5% per year, and (c) less than one electrical cardioversion per year. Lower rate was set at 70 b.p.m. Additional AF prevention and termination features were used in case of no success.After a median follow-up of 18 (10–55) months, therapy was effective in 19 of the 36 included patients (53%). In 74% of the successfully treated patients, additional antiarrhythmic drugs were used. In successfully treated patients, the AF burden was reduced from 15% (5–100%) to 0% (0–4%). Multivariate analysis showed that the concomitant use of a Class I or III antiarrhythmic drug, a lower AF burden before implantation and the use of an angiotensin converting enzyme inhibitor were predictors of successful
TL;DR: The data indicate that younger patients with pharmacologically refractory atrial fibrillation more often undergo non-pharmacological intervention, and neuroticism would not appear to play an important role in the decision to perform a non- PHARMACEUTICAL intervention.