Paddy M. Barrett

Comparison of 24-hour Holter Monitoring with 14-day Novel Adhesive Patch Electrocardiographic Monitoring

BACKGROUND Cardiac arrhythmias are remarkably common and routinely go undiagnosed because they are often transient and asymptomatic. Effective diagnosis and treatment can substantially reduce the morbidity and mortality associated with cardiac arrhythmias. The Zio Patch (iRhythm Technologies, Inc, San Francisco, Calif) is a novel, single-lead electrocardiographic (ECG), lightweight, Food and Drug Administration-cleared, continuously recording ambulatory adhesive patch monitor suitable for detecting cardiac arrhythmias in patients referred for ambulatory ECG monitoring. METHODS A total of 146 patients referred for evaluation of cardiac arrhythmia underwent simultaneous ambulatory ECG recording with a conventional 24-hour Holter monitor and a 14-day adhesive patch monitor. The primary outcome of the study was to compare the detection arrhythmia events over total wear time for both devices. Arrhythmia events were defined as detection of any 1 of 6 arrhythmias, including supraventricular tachycardia, atrial fibrillation/flutter, pause greater than 3 seconds, atrioventricular block, ventricular tachycardia, or polymorphic ventricular tachycardia/ventricular fibrillation. McNemars tests were used to compare the matched pairs of data from the Holter and the adhesive patch monitor. RESULTS Over the total wear time of both devices, the adhesive patch monitor detected 96 arrhythmia events compared with 61 arrhythmia events by the Holter monitor (P < .001). CONCLUSIONS Over the total wear time of both devices, the adhesive patch monitor detected more events than the Holter monitor. Prolonged duration monitoring for detection of arrhythmia events using single-lead, less-obtrusive, adhesive-patch monitoring platforms could replace conventional Holter monitoring in patients referred for ambulatory ECG monitoring.

A prospective randomized trial examining health care utilization in individuals using multiple smartphone-enabled biosensors

Background. Mobile health and digital medicine technologies are becoming increasingly used by individuals with common, chronic diseases to monitor their health. Numerous devices, sensors, and apps are available to patients and consumers–some of which have been shown to lead to improved health management and health outcomes. However, no randomized controlled trials have been conducted which examine health care costs, and most have failed to provide study participants with a truly comprehensive monitoring system. Methods. We conducted a prospective randomized controlled trial of adults who had submitted a 2012 health insurance claim associated with hypertension, diabetes, and/or cardiac arrhythmia. The intervention involved receipt of one or more mobile devices that corresponded to their condition(s) (hypertension: Withings Blood Pressure Monitor; diabetes: Sanofi iBGStar Blood Glucose Meter; arrhythmia: AliveCor Mobile ECG) and an iPhone with linked tracking applications for a period of 6 months; the control group received a standard disease management program. Moreover, intervention study participants received access to an online health management system which provided participants detailed device tracking information over the course of the study. This was a monitoring system designed by leveraging collaborations with device manufacturers, a connected health leader, health care provider, and employee wellness program–making it both unique and inclusive. We hypothesized that health resource utilization with respect to health insurance claims may be influenced by the monitoring intervention. We also examined health-self management. Results & Conclusions. There was little evidence of differences in health care costs or utilization as a result of the intervention. Furthermore, we found evidence that the control and intervention groups were equivalent with respect to most health care utilization outcomes. This result suggests there are not large short-term increases or decreases in health care costs or utilization associated with monitoring chronic health conditions using mobile health or digital medicine technologies. Among secondary outcomes there was some evidence of improvement in health self-management which was characterized by a decrease in the propensity to view health status as due to chance factors in the intervention group.

Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research

Summary Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care.

The fibrillin-1 gene: unlocking new therapeutic pathways in cardiovascular disease

The dramatic reductions in DNA sequencing costs allow us to delve deeper into the genomic alterations that increase susceptibility to many polygenic cardiovascular diseases. One such condition is an abnormal proximal aorta. Until recently, many believed that dilated, distorted or dissected proximal aortas might represent a forme fruste of Marfan syndrome or a continuum of aortopathy. Although an FBN-1 mutation does not guarantee the diagnosis of Marfan syndrome it is clear however that FBN-1 mutations independently confer additional risk for many of the cardiovascular complications classically associated with the disease. Furthermore, treatment with an angiotensin receptor blocker has proven effective in reducing rates of thoracic aortic root dilatation in preliminary studies of Marfan syndrome patients. Awareness of an FBN-1 mutation then highlights the need for increased vigilance for the associated cardiovascular phenotypes. Knowledge of an FBN-1 gene mutation may allow actionable interventions earlier in the natural history of the condition.

Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study

Background Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. Methods and findings Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27–7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. Conclusions Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. Trial registration ClinicalTrials.gov NCT01970969

Pharmacogenetics: Point-of-care genetic testing--a new frontier explored.

Much debate surrounds the utility of CYP2C19*2 genotyping in patients receiving clopidogrel after coronary artery stenting. The effectiveness of its use in a point-of-care setting has now been examined and, given the substantial incremental suppression of platelet reactivity achieved, its routine use might soon be a reality.

The connected health of cardiovascular medicine: Current status and future directions

The technologies of cardiovascular connected health stand to dramatically alter the management and prevention of cardiovascular disease, a worldwide leading cause of death. The American Heart Association has outlined seven key health metrics including physical activity, adequate blood pressure control, weight and a healthy diet, which lie at the core of cardiovascular disease management. Controlling these metrics has been demonstrated to result in substantial reductions in cardiovascular mortality. These metrics are ideally suited to a connected health management strategy involving enhanced patient empowerment and augmented physician engagement. As more patients and healthcare providers adopt technologies that allow for self-monitoring and point-of-care diagnostics, the physician has access to a greater depth of data concerning their patients health and how best to influence it.

Pharm-Econogenomics: A New Appraisal

Pharmacogenomics is poised to radically alter the way drugs are designed, developed, and prescribed. Given that much of the variation in drug response can be attributed to genetic differences, tailoring drugs to an individuals unique genetic signature provides the opportunity to reduce adverse drug events, improve drug efficacy, optimize trial design, and prevent costly drug recalls (1). Developing pharmacogenomic strategies to address these issues is critical, given that lack of efficacy and adverse drug events cost the US well over

Pharmacogenomics in Interventional Pharmacology: Present Status and Future Directions

100 billion annually and that the overall cost for developing a single drug now exceeds

Identification of paroxysmal atrial fibrillation subtypes in over 13,000 individuals

1 billion (2–4). Although genomewide association studies have identified, in general, common sequence variants with increased risks in susceptibility of only 10%–20%, the odds ratios for major side effects or drug responsiveness have been exceptionally large, such as 3- to 20-fold (an increase in risk of 300% to 2000%). This large difference is likely attributable to the fact that humans have been exposed, in evolutionary terms, to most drugs only for a relatively short period of time and that limited genetic selection pressures have been applied (4). Accordingly, exploiting the marked interaction of the genome with drug response represents an exceptional opportunity to enhance the precision and lower the costs of prescription medications. This opportunity has been enhanced by the plummeting cost of sequencing and the recent precedents of accelerated regulatory drug approvals for breakthrough medications developed with genomic guidance (5). Although pharmacogenomics offers the prospect of distinct improvements in drug development and utilization, it is appropriate to ask whether this approach will be cost-effective. In this issue of Clinical Chemistry , Arnaout et al. describe a cost-effectiveness analysis of the costs and time scales involved in the discovery of pharmacogenomic variants, their validation, and their incorporation into future clinical guidelines (3 …