Abstract Classically, the 3 pillars of atrial fibrillation (AF) management have included anticoagulation for prevention of thromboembolism, rhythm control, and rate control. In both prevention and ...management of AF, a growing body of evidence supports an increased role for comprehensive cardiac risk factor modification (RFM), herein defined as management of traditional modifiable cardiac risk factors, weight loss, and exercise. In this narrative review, we summarize the evidence demonstrating the importance of each facet of RFM in AF prevention and therapy. Additionally, we review emerging data on the importance of weight loss and cardiovascular exercise in prevention and management of AF.
Objective Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably ...detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). Study Design This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). Results MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. Conclusion High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.
Myocardial fat deposition (FAT-DEP) has been frequently observed in regions of chronic myocardial infarction in patients with ischemic cardiomyopathy. The role of FAT-DEP within scar-related ...ventricular tachycardia (VT) circuits has not been investigated.
This pilot study aimed to assess the impact of myocardial FAT-DEP on local electrograms and VT circuits in patients with ischemic cardiomyopathy.
Contrast-enhanced computed tomography was performed in 22 patients with ischemic VT. Electroanatomic map points were registered to the corresponding contrast-enhanced computed tomography images. Myocardial FAT-DEP was identified and characterized using a postprocessing image overlay that highlighted areas below 0 Hounsfield units (HU). The mean attenuation of local myocardial regions corresponding to sampled electrograms was measured on short-axis images. The associations of mean attenuation with bipolar and unipolar amplitudes, left ventricular wall thickness, and VT circuit sites were investigated.
Of 1801 electroanatomic map points, 519 (28.8%) were located in regions with FAT-DEP. Significant differences were observed in mean intensity (23.2 ± 35.6 HU vs 81.7 ± 21.9 HU; P < .001), bipolar (0.75 ± 0.83 mV vs 2.9 ± 2.4 mV; P < .001) and unipolar (3.1 ± 1.7 mV vs 7.4 ± 4.3 mV; P < .001) amplitudes, and left ventricular wall thickness (5.2 ± 1.7 mm vs 8.2 ± 2.5 mm; P < .001) between regions with and without FAT-DEP. Lower HU was strongly associated with lower bipolar and unipolar amplitudes (P < .0001, respectively). Importantly, FAT-DEP was associated with critical VT circuit sites with fractionated or isolated potentials.
FAT-DEP was associated with electrogram characteristics and VT circuit sites. Further work will be needed to determine whether FAT-DEP plays a causal role in the generation of ischemic scar-related VT circuits.
A need exists to develop alternative approaches to VT ablation that provide an improved delineation of the arrhythmogenic substrate.
The aim of this study was to evaluate the hypotheses that: (1) the ...heterogeneous zone (HZ, a mixture of normal-appearing tissue and scar) in magnetic resonance imaging (MRI) contains the critical isthmus(es) for ventricular tachycardia (VT), (2) successful ablation of VT would include ablation in the HZ, and (3) inadequate ablation of HZ allows for VT recurrence.
MRI and an electrophysiology study (EP) were performed in a model of chronic myocardial infarction in 17 pigs. In animals that were inducible for VT, ablations were done guided by standard EP criteria and blinded to the MRI. After ablation, electroanatomic mapping results were co-registered with MRI.
In 8 animals, 22 sustained monomorphic VTs were generated. The HZ was substantially larger in inducible (n = 8) compared with noninducible animals (n = 9) 25% ± 10% vs 13% ± 5% of total scar, respectively, P = .007. Acutely, all targeted VTs were successfully ablated, and postprocedure analysis showed that at least 1 ablation was in the HZ in each animal. In 5 animals, a second EP and MRI were performed 1 week after ablation. Three animals had inducible VTs, and MRI showed that the HZ had not been completely ablated. In contrast, the 2 animals without inducible VT revealed no remaining HZ.
These findings show that MRI can define an HZ and determine the location of ablated lesions. The HZ may be a promising ablation target to cure ischemic VTs. Remnants of HZ after ablation may be the substrate for clinical relapses.
Objective The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies ...to date are retrospective. We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection. Study Design A prospective randomized multicenter trial of 27 hospitals was performed. Patients included were those with cerclage placement at ≤23 weeks 6 days in singleton or twin pregnancies, with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized to retention or removal of cerclage. Patients were then expectantly managed and delivered only for evidence of labor, chorioamnionitis, fetal distress, or other medical or obstetrical indications. Management after 34 weeks was at the clinician's discretion. Results The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis, futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis, 32 to removal and 24 to retention of cerclage. There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal 18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32, 25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30, 56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or gestational age at delivery (removal mean 200 days; retention mean 198 days). Conclusion Statistically significant differences were not seen in prolongation of latency, infection, or composite neonatal outcomes. However, there was a numerical trend in the direction of less infectious morbidity, with immediate removal of cerclage. These findings may not have met statistical significance if the original sample size of 142 was obtained, however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention.
Introduction Document Development Process Writing Committee Organization The writing committee was selected to represent the American College of Cardiology (ACC) and the Heart Rhythm Society (HRS) ...and included a cardiovascular training program director, an electrophysiology (EP) program training director, early-career experts, highly experienced specialists representing both the academic and community-based practice settings, and physicians experienced in defining and applying training standards according to the 6 general competency domains promulgated by the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS) and endorsed by the American Board of Internal Medicine (ABIM). Name Employment Representation Consultant Speakers Bureau Ownership/Partnership/Principal Personal Research Institutional/Organizational or Other Financial Benefit Expert Witness Richard Kovacs Indiana University, Krannert Institute of Cardiology--Q.E. and Sally Russell Professor of Cardiology Official Reviewer, ACC Board of Trustees None None None None None None Dhanunjaya Lakkireddy Kansas University Cardiovascular Research Institute Official Reviewer, ACC Board of Governors None None None None None None Howard Weitz Thomas Jefferson University Hospital--Director, Division of Cardiology; Sidney Kimmel Medical College at Thomas Jefferson University--Vice Chair, Department of Medicine Official Reviewer, Competency Management Committee Lead Reviewer None None None None None None Bradley P. Knight Northwestern Medical Center Division of Cardiology--Director, Clinical Cardiac Electrophysiology Organizational Reviewer, Heart Rhythm Society None None None None None None Kousik Krishnan Rush University Medical Center--Associate Professor, Medicine; Director, Arrhythmia Device Clinic Organizational Reviewer, Heart Rhythm Society None None None None None None Kenneth Ellenbogen VCU Medical Center--Director, Clinical Electrophysiology Laboratory Content Reviewer, Cardiology Training and Workforce Committee None None None None None None Michael Emery Greenville Health System Content Reviewer, Sports and Exercise Cardiology Section Leadership Council None None None None None None N.A. Mark Estes Tufts University School of Medicine--Professor, Medicine Content Reviewer, Individual None None None None None None Bulent Gorenek Eskisehir Osmangazi University Medical School Content Reviewer, Electrophysiology Section Leadership Council None None None None None None Larry Jacobs Lehigh Valley Health Network, Division of Cardiology; University of South Florida--Professor, Cardiology Content Reviewer, Cardiology Training and Workforce Committee None None None None None None Andrew Kates Washington University School of Medicine Content Reviewer, Academic Cardiology Section Leadership Council None None None None None None Kristen Patton University of Washington Content Reviewer, Electrophysiology Section Leadership Council None None None None None None Table 3 Core Cardiac Arrhythmia and Electrophysiology Curriculum Training for 3-Year Cardiovascular Fellowship Training Program CIED = cardiac implantable electrical device.
On the basis of this information, the writing committee was constituted to ensure that the Chair and a majority of members have no relevant RWI.\n Miles University of Florida--Professor of Medicine ...Content Reviewer, EP Training Program Director None None None Medtronic UCSF/ZOLL Medical Boston Scientificlow * Medtroniclow * St. Jude Medicallow * None Maged Nageh Kaiser Permanente Los Angeles Medical Center--Attending Physician; Clinical Cardiac Electrophysiology Program Director Content Reviewer, EP Training Program Director None None None None None None Duy Thai Nguyen University of Colorado--Electrophysiology Training Program Director Content Reviewer, EP Training Program Director None None None None None None Kristen K. Patton University of Washington--Associate Professor of Medicine Content Reviewer, ACC EP Section Leadership Council None None None None None None Marwan Refaat American University of Beirut Medical Center--Assistant Professor of Medicine Content Reviewer, ACC EP Section Leadership Council None None None None None None Lynda Rosenfeld Yale University School of Medicine--Director, Yale University Clinical Cardiac Electrophysiology Fellowship Program Content Reviewer, EP Training Program Director None None None Medtronicdagger Boston Scientificlow * Medtroniclow * St. Jude Medicallow * None Peter Santucci Loyola University-- Electrophysiology Training Program Director; Professor of Medicine Content Reviewer, EP Training Program Director None None None None Biosense Websterlow * Biotroniklow * Boston Scientificlow * Medtroniclow * None Komandoor Srivathsan Mayo Clinic--Associate Professor, College of Medicine Content Reviewer, EP Training Program Director St. Jude Medical Biosense Webster None None None None Gregory Supple University of Pennsylvania Health System--Associate Director, Cardiac Electrophysiology Fellowship Program; Assistant Professor of Clinical Medicine Content Reviewer, EP Training Program Director Biotronik St. Jude Medical None None Boston Scientific Medtronic None None Gaurav A. Upadhyay University of Chicago--Assistant Professor of Medicine Content Reviewer, ACC EP Section Leadership Council Biosense Webster Biotronik Boston Scientific Medtronic None None None None None * This table reflects peer reviewers' relationships with industry and other entities that were reported and deemed to be relevant to this document, as well as employment, representation in the review process, and reporting categories.
Objective Preterm rupture of membranes (PROM) is associated with an increased risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone caproate (17OHP-C) reduces the risk of ...preterm birth in some women who are at risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy or improve perinatal outcome when given to mothers with preterm rupture of the membranes. Study Design This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. The study included singleton pregnancies with gestational ages from 230/7 to 306/7 weeks at enrollment, documented PROM, and no contraindication to expectant management. Consenting women were assigned randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or placebo. The primary outcome was continuation of pregnancy until a favorable gestational age, which was defined as either 340/7 weeks of gestation or documentation of fetal lung maturity at 320/7 to 336/7 weeks of gestation. The 2 prespecified secondary outcomes were interval from randomization to delivery and composite adverse perinatal outcome. The planned sample size was 222 total women. Results From October 2011 to April 2014, 152 women were enrolled; 74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to placebo. The trial was stopped when results of a planned interim analysis suggested that continuation was futile. The primary outcome was achieved in 3% of the 17OHP-C group and 8% of the placebo group ( P = .18). There was no significant between-group difference in the prespecified secondary outcomes, randomization-to-delivery interval (17.1 ± 16.1 vs 17.0 ± 15.8 days, respectively; P = .76) or composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No significant differences were found in other outcomes, which included rates of chorioamnionitis, postpartum endometritis, cesarean delivery, individual components of the composite outcome, or prolonged neonatal length of stay. Conclusion Compared with placebo, weekly 17OHP-C injections did not prolong pregnancy or reduce perinatal morbidity in patients with PROM in this trial.
Abstract Largely on the basis of the first publication of findings of net harm with menopausal hormone treatment in the Women's Health Initiative (WHI) hormone trials, current Food and Drug ...Administration recommendations limit menopausal hormone treatment to the “… shortest duration consistent with treatment goals …,” with goals generally taken to mean relief of menopausal symptoms and maximal duration as approximately 5 years. The WHI finding of net harm was due largely to the absence of beneficial effects on coronary heart disease incidence rates. Published analyses of WHI data by age or time since menopause find that excess coronary heart disease risk with menopausal hormone treatment is confined to more remotely menopausal or older women, with younger women showing nonsignificant trends toward benefit (the “timing hypothesis”). Moreover, a recently published reexamination of data from the WHI Estrogen plus Progestin trial suggests that reduced coronary heart disease risk may appear only after 5 to 6 years of treatment. Consistent with this finding, risk ratios for coronary heart disease were calculated as 1.08 (95% confidence interval, 0.86-1.36) in years 1 to 6 and as 0.46 (confidence interval, 0.28-0.78) in years 7 to 8+ in the WHI Estrogen Alone trial. Previous studies also support the beneficial effects of menopausal hormone treatment after prolonged exposure. Thus, current analyses do not support a generalized recommendation for short duration of menopausal hormone treatment. Rather, they suggest that current Food and Drug Administration practice guidelines should be reconsidered to allow individualized care based on risk:benefit considerations. New research is urgently needed evaluating influences of timing, duration, dose, route of administration, and agents on menopausal hormone treatment-related risks and benefits to better understand how to optimize recommendations for individual patients.
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