Influence of Multimorbidity on Burden and Appropriateness of Implantable Cardioverter-Defibrillator Therapies.

Objective: To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies.

Design: Retrospective cohort study.

Setting: Seven US healthcare delivery systems.

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network.

Background: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems.

Methods And Results: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

Background: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention.

Kidney function and appropriateness of device therapies in adults with implantable cardioverter defibrillators.

Objective: Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD.

Methods: We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators.

Effect of omega-three polyunsaturated fatty acids on inflammation, oxidative stress, and recurrence of atrial fibrillation.

The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study.

Topical timolol for treatment of epistaxis in hereditary haemorrhagic telangiectasia associated with bradycardia: a look at CYP2D6 metabolising variants.

A 59-year-old man presented to the emergency department with lightheadedness. He had started intranasal administration of ophthalmic timolol for the prevention of epistaxis associated with hereditary haemorrhagic telangiectasia approximately 3 weeks earlier with excellent response. His heart rate was about half its normal rate, an ECG revealed sinus bradycardia, and it was determined he had significant cardiac issues in his family history.

Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors.

Dabigatran has been associated with greater risk of myocardial infarction (MI) than warfarin. It is unknown whether the increased risk is unique to dabigatran, an adverse effect shared by other oral direct thrombin inhibitors (DTIs), or the result of a protective effect of warfarin against MI. To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization.

Predicting atrial fibrillation and flutter using electronic health records.

Electronic Health Records (EHR) contain large amounts of useful information that could potentially be used for building models for predicting onset of diseases. In this study, we have investigated the use of free-text and coded data in Marshfield Clinic's EHR, individually and in combination for building machine learning based models to predict the first ever episode of atrial fibrillation and/or atrial flutter (AFF). We trained and evaluated our AFF models on the EHR data across different time intervals (1, 3, 5 and all years) prior to first documented onset of AFF.

Longitudinal study of implantable cardioverter-defibrillators: methods and clinical characteristics of patients receiving implantable cardioverter-defibrillators for primary prevention in contemporary practice.

Background: Implantable cardioverter-defibrillators (ICDs) are increasingly used for primary prevention after randomized, controlled trials demonstrating that they reduce the risk of death in patients with left ventricular systolic dysfunction. The extent to which the clinical characteristics and long-term outcomes of unselected, community-based patients with left ventricular systolic dysfunction undergoing primary prevention ICD implantation in a real-world setting compare with those enrolled in the randomized, controlled trials is not well characterized. This study is being conducted to address these questions.

A Collective Ranking Method for Genome-wide Association Studies.

Genome-wide association studies (GWAS) analyze genetic variation (SNPs) across the entire human genome, searching for SNPs that are associated with certain phenotypes, most often diseases, such as breast cancer. In GWAS, we seek a ranking of SNPs in terms of their relevance to the given phenotype. However, because certain SNPs are known to be highly correlated with one another across individuals, it can be beneficial to take into account these correlations when ranking.

Discrimination against international medical graduates in the United States residency program selection process.

Background: Available evidence suggests that international medical graduates have improved the availability of U.S. health care while maintaining academic standards.

Atrial flutter versus atrial fibrillation in a general population: differences in comorbidities associated with their respective onset.

Objective: Determine and compare the prevalence of known risk factors for cardiovascular disease among unselected individuals presenting with their first ever episode of atrial flutter (AFL) and atrial fibrillation (AF).

Study Design And Setting: We evaluated 11 pre-selected clinical variables including age, sex, smoking history and other potential cardiac risk factors. Using the resources of the Marshfield Epidemiologic Study Area, a population-based database, all newly diagnosed cases of either AFL or AF in the region during a 4-year period were identified.

Use of implantable cardioverter defibrillators for primary prevention in the community: do women and men equally meet trial enrollment criteria?

Background: Fewer women than men undergo implantable cardioverter defibrillator (ICD) implantation for the primary prevention of sudden cardiac death. The criteria used to select patients for ICD implantation may be more permissive among men than for women. We hypothesized that women who undergo primary prevention ICD implantation more often meet strict trial enrollment criteria for this therapy.

Gender differences in procedure-related adverse events in patients receiving implantable cardioverter-defibrillator therapy.

Background: Women are at higher risk than men for adverse events with certain invasive cardiac procedures. Our objective was to compare rates of in-hospital adverse events in men and women receiving implantable cardioverter- defibrillator (ICD) therapy in community practice.

Methods And Results: Using the National Cardiovascular Data Registry ICD Registry, we identified patients undergoing first-time ICD implantation between January 2006 and December 2007.

CYP4F2 genetic variant alters required warfarin dose.

Warfarin is an effective, commonly prescribed anticoagulant used to treat and prevent thrombotic events. Because of historically high rates of drug-associated adverse events, warfarin remains underprescribed. Further, interindividual variability in therapeutic dose mandates frequent monitoring until target anticoagulation is achieved.

Assessing the impact of censoring of costs and effects on health-care decision-making: an example using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

Objectives: Losses to follow-up and administrative censoring can cloud the interpretation of trial-based economic evaluations. A number of investigators have examined the impact of different levels of adjustment for censoring, including nonadjustment, adjustment of effects only, and adjustment for both costs and effects. Nevertheless, there is a lack of research on the impact of censoring on decision-making.

Prevalence and mortality of patients with myocardial infarction and reduced left ventricular ejection fraction in a defined community: relation to the second multicenter automatic defibrillator implantation trial.

Objectives: We compared characteristics and mortality of patients from a community population meeting enrollment criteria of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT II) to those of the MADIT II subjects.

Background: MADIT II showed that implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with myocardial infarction (MI) and low left ventricular ejection fraction (LVEF)
Methods: We used the resources of the Marshfield Epidemiologic Study Area (MESA), a well defined geographic region to identify MADIT II-type patients and determined outcomes during a 2-year follow-up period.

Evaluation of genetic factors for warfarin dose prediction.

Objectives: Warfarin is a commonly prescribed anticoagulant drug used to prevent thromboses that may arise as a consequence of orthopedic and vascular surgery or underlying cardiovascular disease. Warfarin is associated with a notoriously narrow therapeutic window where small variations in dosing may result in hemorrhagic or thrombotic complications. To ultimately improve dosing of warfarin, we evaluated models for stable maintenance dose that incorporated both clinical and genetic factors.

Implantable cardiac defibrillator placement in a patient with persistent left superior vena cava and Brugada syndrome.

A 45-year-old man was diagnosed with new-onset atrial fibrillation. Control of ventricular rate led to spontaneous conversion to sinus rhythm. Subsequent electrocardiograms revealed ST segment changes characteristic of Brugada syndrome.

Impact of age, CYP2C9 genotype and concomitant medication on the rate of rise for prothrombin time during the first 30 days of warfarin therapy.

Objectives: To characterize the impact of several important clinical variables on the rate of anticoagulation during warfarin initiation (i.e., the first 30 days).

Comparison of management patterns and clinical outcomes in patients with atrial fibrillation in Canada and the United States (from the analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] database).

Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada.

A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data.

Background: Rapid genetic screening for cytochrome P450 (CYP) 2C9 variants may play a role in improving the efficacy and safety of warfarin in individuals with CYP2C9 variants. The feasibility of prospective CYP2C9 model-based warfarin dosing has not yet been assessed.

Objectives: To evaluate the feasibility of applying a CYP2C9 gene-based warfarin dosing model in clinical practice.

Asymptomatic atrial fibrillation: demographic features and prognostic information from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

Background: Atrial fibrillation (AF) may occur without symptoms. Little is known about demographic features and prognostic information in patients with asymptomatic AF.

Methods: In the AFFIRM study, 4060 patients were randomized to either rhythm or rate control.

Hyperventilation-induced syncope: no need to panic.

Accurately diagnosing and treating adult patients presenting with recurrent syncope can be extremely problematic. We present the case of a patient who presented with recurrent syncope. We propose that many cases currently classified as idiopathic may in fact be due to orthostatic hypotension secondary to hyperventilation, or simply hyperventilation-induced syncope.