Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation

Background: Cryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI. Methods: We included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase >= 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response. Results: Following PVI, mean HR +/- standard deviation increased in the entire group from 63.5 +/- 8.4 to 69.1 +/- 9.9 bpm at 3 months (p < 0.001), and to 71.9 +/- 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 +/- 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 +/- 10.6 bpm (pre-ablation), 84.6 +/- 9.8 bpm (3 months), 80.1 +/- 6.5 bpm (6 months) and 76.3 +/- 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation. Conclusion: Few patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year

A Mycobacterium tuberculosis cluster demonstrating the use of genotyping in urban tuberculosis control

Background: DNA fingerprinting of Mycobacterium tuberculosis isolates offers better opportunities to study links between tuberculosis (TB) cases and can highlight relevant issues in urban TB control in low-endemic countries. Methods: A medium-sized molecular cluster of TB cases with identical DNA fingerprints was used for the development of a visual presentation of epidemiologic links between cases. Results: Of 32 cases, 17 (53%) were linked to the index case, and 11 (34%) to a secondary case. The remaining four (13%) could not be linked and were classified as possibly caused by the index patient. Of the 21 cases related to the index case, TB developed within one year of the index diagnosis in 11 patients (52%), within one to two years in four patients (19%), and within two to five years in six patients (29%). Conclusion: Cluster analysis underscored several issues for TB control in an urban setting, such as the recognition of the outbreak, the importance of reinfections, the impact of delayed diagnosis, the contribution of pub-related transmissions and its value for decision-making to extend contact investigations. Visualising cases in a cluster diagram was particularly useful in finding transmission locations and the similarities and links between patients

Micronutrient deficiencies and new-onset atrial fibrillation in a community-based cohort:data from PREVEND

Aim: Malnutrition has been linked to cardiovascular diseases. Both selenium and iron deficiency have been associated with worse prognosis in patients with heart failure (HF). Yet, little is known about the role of micronutrients in the development of atrial fibrillation (AFib). In this study, we aimed to elucidate the association of micronutrient deficiencies with new-onset AFib. Methods: Selenium, magnesium, and iron parameters were measured in a well-characterized prospective cohort study (N = 5452). Selenium deficiency was defined as serum selenium &lt; 70 μg/L, iron deficiency as serum ferritin &lt; 30 μg/L, and magnesium deficiency as plasma magnesium &lt; 0.85 mmol/L. New-onset AFib was the primary outcome. Additionally, we tested for previously reported effect-modifiers where applicable. Results: Selenium, iron, and magnesium deficiency was observed in 1155 (21.2%), 797 (14.6%), and 3600 (66.0%) participants, respectively. During a mean follow-up of 6.2 years, 136 (2.5%) participants developed new-onset AFib. Smoking status significantly interacted with selenium deficiency on outcome (p = 0.079). After multivariable adjustment for components of the CHARGE-AF model, selenium deficiency was associated with new-onset AFib in non-smokers (HR 1.69, 95% CI 1.09–2.64, p = 0.020), but not in smokers (HR 0.78, 95% CI 0.29–2.08, p = 0.619). Magnesium deficiency (HR 1.40, 95% CI 0.93–2.10, p = 0.110) and iron deficiency (HR 0.62, 95% CI 0.25–1.54, p = 0.307) were not significantly associated with new-onset AFib. Conclusion: Selenium deficiency was associated with new-onset AFib in non-smoking participants. Interventional studies that investigate the effects of optimizing micronutrients status in a population at risk are needed to assess causality, especially in those with selenium deficiency. Graphical abstract: Micronutrients deficiencies (selenium, iron, and magnesium) have been associated with cardiovascular diseases and mitochondrial dysfunction in human cardiomyocytes. However, it is not known whether these deficiencies are associated with atrial fibrillation. To investigate this question, we measured all three micronutrients in 5452 apparently healthy individuals. After a mean follow-up of 6.2 years, there were 136 participants who developed atrial fibrillation. Participants with selenium deficiency had a significant increased risk to develop atrial fibrillation, as did the participants with two or more deficiencies. [Figure not available: see fulltext.]</p

The effect of watchful waiting compared to immediate test ordering instructions on general practitioners' blood test ordering behaviour for patients with unexplained complaints; a randomized clinical trial (ISRCTN55755886)

<p>Abstract</p> <p>Background</p> <p>Immediate blood testing for patients presenting with unexplained complaints in family practice is superfluous from a diagnostic point of view. However, many general pracitioners (GPs) order tests immediately. Watchful waiting reduces the number of patients to be tested and the number of false-positive results. The objectives of this study are: to determine the feasibility of watchful waiting compared to immediate test ordering; to determine if a special quality improvement strategy can improve this feasibility; and to determine if watchful waiting leads to testing at a later time.</p> <p>Methods</p> <p>The study is a cluster-randomized clinical trial with three groups, on blood test ordering strategies in patients with unexplained complaints. GPs in group one were instructed to order tests immediately and GPs in group two to apply a watchful waiting approach. GPs in group three received the same instruction as group two, but they were supported by a systematically designed quality improvement strategy. A total of 498 patients with unexplained complaints from 63 practices of Dutch GPs participated. We measured: the percentage of patients for whom tests were ordered and number of tests ordered at the first consultation; performance on the strategy's performance objectives (i.e., ordering fewer tests and specific communication skills); the number of tests ordered after four weeks; and GP and patient characteristics.</p> <p>Results</p> <p>Immediate test ordering proved feasible in 92% of the patients; watchful waiting in 86% and 84%, respectively, for groups two and three. The two watchful waiting groups did not differ significantly in the achievement of any of the performance objectives. Of the patients who returned after four weeks, none from group one and six from the two watchful waiting groups had tests ordered for them.</p> <p>Conclusions</p> <p>Watchful waiting is a feasible approach. It does not lead to testing immediately afterwards. Furthermore, watchful waiting was not improved by the quality improvement strategy.</p> <p>Trial registration</p> <p>Clinical trial registration: <a href="http://www.controlled-trials.com/ISRCTN55755886">ISRCTN55755886</a></p

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis. METHODS: We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts. RESULTS: Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes. CONCLUSIONS: Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies

Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.</p> <p>Methods and design</p> <p>7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods.</p> <p>Discussion</p> <p>This study will provide further evidence to enable decision making in population screening for colorectal cancer.</p> <p>Trial registration</p> <p>Dutch trial register: NTR1829</p

Unsuspected and extensive transmission of a drug-susceptible Mycobacterium tuberculosis strain

<p>Abstract</p> <p>Background</p> <p>A large and unsuspected tuberculosis outbreak involving 18.7% of the total of the tuberculosis cases studied, was detected in a population-based molecular epidemiological study performed in Zaragoza (Spain) from 2001 to 2004.</p> <p>Methods</p> <p>The <it>Mycobacterium tuberculosis </it>drug-susceptible strain, named <it>MTZ </it>strain, was genetically characterized by IS<it>6110</it>-RFLP, Spoligotyping and by MIRU-VNTR typing and the genetic patterns obtained were compared with those included in international databases. The characteristics of the affected patients, in an attempt to understand why the <it>MTZ </it>strain was so highly transmitted among the population were also analyzed.</p> <p>Results</p> <p>The genetic profile of the <it>MTZ </it>strain was rare and not widely distributed in our area or elsewhere. The patients affected did not show any notable risk factor for TB.</p> <p>Conclusion</p> <p>The <it>M. tuberculosis </it>strain <it>MTZ</it>, might have particular transmissibility or virulence properties, and we believe that greater focus should be placed on stopping its widespread dissemination.</p

The effectiveness of "Exercise on Prescription" in stimulating physical activity among women in ethnic minority groups in the Netherlands: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Lack of physical activity is an important risk factor for overweight, diabetes, cardiovascular disease and other chronic conditions. In the Netherlands, ethnic minority groups are generally less physically active and rate their own health poorer compared to ethnic Dutch. This applies in particular to women. For this reason women from ethnic minority groups are an important target group for interventions to promote physical activity.</p> <p>In the Netherlands, an exercise referral program ("Exercise on Prescription") seems successful in reaching women from ethnic minority groups, in particular because of referral by the general practitioner and because the program fits well with the needs of these women. However, the effect of the intervention on the level of physical activity and related health outcomes has not been formally evaluated within this population. This paper describes the study design for the evaluation of the effect of "Exercise on Prescription" on level of physical activity and related health outcomes.</p> <p>Methods</p> <p>The randomized controlled trial will include 360 inactive women from ethnic minority groups, with the majority having a non-Western background, aged between 18 and 65 years old, with regular visits to their general practitioner. Participants will be recruited at healthcare centres within a deprived neighbourhood in the city of The Hague, the Netherlands.</p> <p>An intervention group of 180 women will participate in an exercise program with weekly exercise sessions during 20 weeks. The control group (n = 180) will be offered care as usual. Measurements will take place at baseline, and after 6 and 12 months. Main outcome measure is minutes of self reported physical activity per week. Secondary outcomes are the mediating motivational factors regarding physical activity, subjective and objective health outcomes (including wellbeing, perceived health, fitness and body size) and use of (primary) health care. Attendance and attrition during the program will be determined.</p> <p>Conclusion</p> <p>This trial will provide information on the effectiveness of an exercise referral scheme on the short and long term among women from ethnic minority groups, mainly non-Western, in the Netherlands. The results of this study will contribute to the evidence base for interventions in ethnic minority populations.</p> <p>Trial registration</p> <p>Dutch Trial register: NTR1294</p

Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation

<p>Abstract</p> <p>Background</p> <p>Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder associated with the partial deletion of integral numbers of 3.3 kb D4Z4 DNA repeats within the subtelomere of chromosome 4q. A number of candidate FSHD genes, adenine nucleotide translocator 1 gene (<it>ANT1</it>), FSHD-related gene 1 (<it>FRG1</it>), <it>FRG2 </it>and <it>DUX4c</it>, upstream of the D4Z4 array (FSHD locus), and double homeobox chromosome 4 (<it>DUX4</it>) within the repeat itself, are upregulated in some patients, thus suggesting an underlying perturbation of the chromatin structure. Furthermore, a mouse model overexpressing <it>FRG1 </it>has been generated, displaying skeletal muscle defects.</p> <p>Results</p> <p>In the context of myogenic differentiation, we compared the chromatin structure and tridimensional interaction of the D4Z4 array and <it>FRG1 </it>gene promoter, and <it>FRG1 </it>expression, in control and FSHD cells. The <it>FRG1 </it>gene was prematurely expressed during FSHD myoblast differentiation, thus suggesting that the number of D4Z4 repeats in the array may affect the correct timing of <it>FRG1 </it>expression. Using chromosome conformation capture (3C) technology, we revealed that the <it>FRG1 </it>promoter and D4Z4 array physically interacted. Furthermore, this chromatin structure underwent dynamic changes during myogenic differentiation that led to the loosening of the <it>FRG1</it>/4q-D4Z4 array loop in myotubes. The <it>FRG1 </it>promoter in both normal and FSHD myoblasts was characterized by H3K27 trimethylation and Polycomb repressor complex binding, but these repression signs were replaced by H3K4 trimethylation during differentiation. The D4Z4 sequences behaved similarly, with H3K27 trimethylation and Polycomb binding being lost upon myogenic differentiation.</p> <p>Conclusion</p> <p>We propose a model in which the D4Z4 array may play a critical chromatin function as an orchestrator of <it>in cis </it>chromatin loops, thus suggesting that this repeat may play a role in coordinating gene expression.</p