Publications by authors named "Joseph G Akar"

64 Publications

Temporal Trends in Arrhythmogenicity Related to Treatment of COVID-19 Infection.

Circ Arrhythm Electrophysiol 2020 10 15;13(10):e008841. Epub 2020 Sep 15.

Department of Internal Medicine, Cardiovascular Medicine, Yale School of Medicine, New Haven (J.P.H., I.M., R.T., R.C., V.K.W., C.J.H., A.D.E., J.G.A.).

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http://dx.doi.org/10.1161/CIRCEP.120.008841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566294PMC
October 2020

Reply to: "QT prolongation with hydroxychloroquine and azithromycin for the treatment of COVID-19: The need for pharmacogenetic insights".

J Cardiovasc Electrophysiol 2020 10 31;31(10):2795. Epub 2020 Aug 31.

Department of Internal Medicine, Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA.

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http://dx.doi.org/10.1111/jce.14721DOI Listing
October 2020

Predictors of Cardiac Perforation With Catheter Ablation of Atrial Fibrillation.

JACC Clin Electrophysiol 2020 06 25;6(6):636-645. Epub 2020 Mar 25.

Duke Clinical Research Institute, Durham, North Carolina, (c)Electrophysiology Section, Duke University Hospital, Durham, North Carolina, USA; Electrophysiology Section, Duke University Hospital, Durham, North Carolina, USA.

Objectives: This study identified factors associated with risk for cardiac perforation in the setting of atrial fibrillation (AF) ablation in contemporary clinical practice.

Background: Cardiac perforation is an uncommon but potentially fatal complication of AF ablation. An improved understanding of factors associated with cardiac perforation could facilitate improvements in procedural safety.

Methods: Logistic regression models were used to assess predictors of cardiac perforation among Medicare beneficiaries who underwent AF ablation from July 1, 2013 and December 31, 2017. Cardiac perforation was defined as a diagnosis of hemopericardium, cardiac tamponade, or pericardiocentesis, within 30 days of AF ablation.

Results: Of 102,398 patients who underwent AF ablation, 0.61% (n = 623) experienced cardiac perforation as a procedural complication. Rates of cardiac perforation decreased over time. In adjusted analyses of the overall population, female sex (odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.14 to 1.58; p = 0.0004), obesity (OR: 1.35; 95% CI: 1.09 to 1.68; p = 0.0050), and absence of intracardiac echocardiography (ICE) (OR: 4.85; 95% CI: 4.11 to 5.71; p < 0.0001) were associated with increased risk for cardiac perforation, whereas previous cardiac surgery (OR: 0.14; 95% CI: 0.07 to 0.26; p < 0.0001) was associated with a lower risk for perforation. Patient risk factors for cardiac perforation were identical in the subset of patients in whom ICE was used (n = 76,134). A risk score was generated with the following point assignments: female sex (1 point); obesity (1 point); nonuse of ICE (5 points); and previous cardiac surgery (-6 points).

Conclusions: Cardiac perforation is a rare complication of AF ablation; incidence has decreased over time. One of the strongest predictors of cardiac perforation in the contemporary era is a modifiable factor, use of intraprocedural ICE.
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http://dx.doi.org/10.1016/j.jacep.2020.01.011DOI Listing
June 2020

Incidence and determinants of QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin.

J Cardiovasc Electrophysiol 2020 08 20;31(8):1904-1907. Epub 2020 Jun 20.

Department of Internal Medicine, Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1111/jce.14594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300464PMC
August 2020

3-Dimensional Transseptal Puncture Based on Electrographic Characteristics of Fossa Ovalis: A Fluoroscopy-Free and Echocardiography-Free Method.

JACC Cardiovasc Interv 2020 05;13(10):1223-1232

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China.

Objectives: This study sought to define electrographic characteristics of the fossa ovalis (FO) and use these findings in developing a 3-dimensional (3D) transseptal puncture (TSP) technique that does not rely on fluoroscopy or echocardiography.

Background: Traditional TSP method based on fluoroscopy or echocardiography is basically a 2-dimensional (2D) technique. A valid 3D method of TSP has not been sufficiently clarified.

Methods: The shape of the FO and its center were "electrographically" defined by comparing their potential characteristics to those of the surrounding limbus. After validation by intracardiac echocardiography, this FO mapping was incorporated into 3D electroanatomical reconstruction of the right atrium. Using a new catheter connection, the transseptal needle could be visualized nonfluoroscopically and directed to the precise localization of the FO on the electroanatomic map.

Results: A total of 276 patients who underwent atrial fibrillation ablation were included. The central FO was identified in all cases with atrial electrogram voltage at 0.33 ± 0.21 mV. The amplitude of atrial potential at the FO annulus was 1.70 ± 0.72 mV (p < 0.001). By incorporating the electrographically defined FO into the 3D electroanatomic mapping and using the transseptal needle visualization approach, TSP was successful in all patients, with 91% of the cases at the first attempt. Atrial fibrillation ablation was completed in all patients with no major complication.

Conclusions: Electrographic characteristics of the FO center are distinct from those of the surrounding regions. This information can be leveraged to define the FO on 3D electroanatomic mappings, thereby facilitating safe TSP without the need of ancillary imaging with fluoroscopy or echocardiography.
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http://dx.doi.org/10.1016/j.jcin.2020.03.015DOI Listing
May 2020

Understanding tricuspid valve remodelling in atrial fibrillation using three-dimensional echocardiography.

Eur Heart J Cardiovasc Imaging 2020 07;21(7):747-755

Laboratory of Echocardiography, Cardiovascular Division, Yale New Haven Hospital, Yale School of Medicine, 20 York Street, New Haven, CT 06510, USA.

Aims: Atrial fibrillation (AF) has been associated with tricuspid annulus (TA) dilation in patients with severe functional tricuspid regurgitation (TR); however, the impact of AF is less clear in patients without severe TR. Our aim was to characterize TA remodelling in patients with AF in the absence of severe TR using 3D transoesophageal echocardiography (TOE).

Methods And Results: Ninety patients underwent clinically indicated transthoracic and TOE: non-structural (NS)-AF (n = 30); AF with left heart disease (LHD) (n = 30), and controls in sinus rhythm (n = 30). Three-dimensional TOE datasets were analysed to measure TA dimensions using novel dedicated tricuspid valve software. The NS-AF group showed biatrial dilatation and normal right ventricular (RV) size with decreased longitudinal function compared to controls, whereas the LHD-AF group showed biatrial dilatation, RV enlargement, decreased biventricular function, and higher systolic pulmonary artery pressure compared with the other groups. Indexed TA area, minimum diameter, maximum diameter, and total perimeter were significantly larger in the NS-AF group than in controls (measurements in end-diastole: 6.4 ± 1.1 vs. 5.0 ± 0.6 cm2/m2, 1.8 ± 0.3 vs. 1.6 ± 0.2 cm/m2, 2.1 ± 0.3 vs. 1.9 ± 0.2 cm/m2, and 6.6 ± 0.9 vs. 5.9 ± 0.7 cm/m2, respectively, all P < 0.05). There was no significant difference in any indexed TA parameter between AF groups. TA circularity index (ratio between minimum and maximal diameters) and TA fractional area change between end-diastole and end-systole were no different among the three groups.

Conclusion: AF is associated with right atrial and tricuspid annular remodelling independent of the presence of LHD in patients with intrinsically normal tricuspid leaflets without severe TR.
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http://dx.doi.org/10.1093/ehjci/jeaa058DOI Listing
July 2020

Aggregating multiple real-world data sources using a patient-centered health-data-sharing platform.

NPJ Digit Med 2020 20;3:60. Epub 2020 Apr 20.

8Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN USA.

Real-world data sources, including electronic health records (EHRs) and personal digital device data, are increasingly available, but are often siloed and cannot be easily integrated for clinical, research, or regulatory purposes. We conducted a prospective cohort study of 60 patients undergoing bariatric surgery or catheter-based atrial fibrillation ablation at two U.S. tertiary care hospitals, testing the feasibility of using a patient-centered health-data-sharing platform to obtain and aggregate health data from multiple sources. We successfully obtained EHR data for all patients at both hospitals, as well as from ten additional health systems, which were successfully aggregated with pharmacy data obtained for patients using CVS or Walgreens pharmacies; personal digital device data from activity monitors, digital weight scales, and single-lead ECGs, and patient-reported outcome measure data obtained through surveys to assess post-procedure recovery and disease-specific symptoms. A patient-centered health-data-sharing platform successfully aggregated data from multiple sources.
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http://dx.doi.org/10.1038/s41746-020-0265-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170944PMC
April 2020

Recurrence quantification analysis of complex-fractionated electrograms differentiates active and passive sites during atrial fibrillation.

J Cardiovasc Electrophysiol 2019 11 2;30(11):2229-2238. Epub 2019 Oct 2.

Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Objectives: To differentiate electrograms representing sites of active atrial fibrillation (AF) drivers from passive ones.

Background: Ablation of complex-fractionated atrial electrograms (CFAEs) is controversial due to difficulty in distinguishing CFAEs representing sites of active AF drivers from passive mechanisms. We hypothesized that active CFAE sites exhibit repetitive wavefront directionality, thereby inscribing an electrogram conformation (Egm-C) that is more recurrent compared with passive CFAE sites; and that can be differentiated from passive CFAEs using nonlinear recurrence quantification analysis (RQA).

Methods: We developed multiple computer models of active CFAE mechanisms (ie, rotors) and passive CFAE mechanisms (ie, wavebreak, slow conduction, and double potentials). CFAE signals were converted into discrete time-series representing Egm-C. The RQA algorithm was used to compare signals derived from active CFAE sites to those from passive CFAEs sites. The RQA algorithm was then applied to human CFAE signals collected during AF ablation (n  =  17 patients).

Results: RQA was performed in silico on simulated bipolar CFAEs within active (n = 45) and passive (n = 60) areas. Recurrence of Egm-C was significantly higher in active compared with passive CFAE sites (31.8% ± 19.6% vs 0.3% ± 0.5%, respectively, P < .0001) despite no difference in mean cycle length (CL). Similarly, for human AF (n = 39 signals), Egm-C recurrence was higher in active vs passive CFAE areas despite similar CLs (%recurrence 13.6% ± 15.5% vs 0.1% ± 0.3%, P < .002; mean CL 102.5 ± 14.3 vs 106.6 ± 14.4, P = NS).

Conclusion: Active CFAEs critical to AF maintenance exhibit higher Egm-C recurrence and can be differentiated from passive bystander CFAE sites using RQA.
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http://dx.doi.org/10.1111/jce.14161DOI Listing
November 2019

Outcomes and costs of remote patient monitoring among patients with implanted cardiac defibrillators: An economic model based on the PREDICT RM database.

J Cardiovasc Electrophysiol 2019 07 29;30(7):1066-1077. Epub 2019 Apr 29.

Yale University School of Medicine and Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut; and on behalf of the NCDR.

Background: Remote monitoring of implantable cardioverter-defibrillators has been associated with reduced rates of all-cause rehospitalizations and mortality among device recipients, but long-term economic benefits have not been studied.

Methods And Results: An economic model was developed using the PREDICT RM database comparing outcomes with and without remote monitoring. The database included patients ages 65 to 89 who received a Boston Scientific device from 2006 to 2010. Parametric survival equations were derived for rehospitalization and mortality to predict outcomes over a maximum time horizon of 25 years. The analysis assessed rehospitalization, mortality, and the cost-effectiveness (expressed as the incremental cost per quality-adjusted life year) of remote monitoring versus no remote monitoring. Remote monitoring was associated with reduced mortality; average life expectancy and average quality-adjusted life years increased by 0.77 years and 0.64, respectively (6.85 life years and 5.65 quality-adjusted life years). When expressed per patient-year, remote monitoring patients had fewer subsequent rehospitalizations (by 0.08 per patient-year) and lower hospitalization costs (by $554 per patient year). With longer life expectancies, remote monitoring patients experienced an average of 0.64 additional subsequent rehospitalizations with increased average lifetime hospitalization costs of $2784. Total costs of outpatient and physician claims were higher with remote monitoring ($47 515 vs $42 792), but average per patient-year costs were lower ($6232 vs $6244). The base-case incremental cost-effectiveness ratio was $10 752 per quality-adjusted life year, making remote monitoring high-value care.

Conclusion: Remote monitoring is a cost-effective approach for the lifetime management of patients with implantable cardioverter-defibrillators.
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http://dx.doi.org/10.1111/jce.13934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850124PMC
July 2019

Atrial Fibrillation Thermographic and Endoscopic Monitoring of Patients: Safety Algorithm for the Esophagus: AF TEMP-SAFE Study.

Circ Arrhythm Electrophysiol 2018 12;11(12):e006814

Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT (A.J.K., A.D.E., J.V.F., J.G.A.).

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http://dx.doi.org/10.1161/CIRCEP.118.006814DOI Listing
December 2018

Luminal esophageal temperature monitoring to reduce esophageal thermal injury during catheter ablation for atrial fibrillation: A review.

Trends Cardiovasc Med 2019 07 19;29(5):264-271. Epub 2018 Sep 19.

Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA. Electronic address:

Over the past decade, catheter ablation for atrial fibrillation has emerged as an important rhythm control strategy. One of the most dreaded complications of this procedure is atrio-esophageal (AE) fistula formation, which is relatively rare but usually fatal. Esophageal tissue injury during ablation appears to be a precursor to the formation of AE fistulae. Luminal esophageal temperature (LET) monitoring is one of the most commonly utilized strategies to mitigate this risk, despite little evidence that it reduces esophageal injury. The incidence of AE fistulae appears to be on the rise, despite the widespread use of LET monitoring. This may be due to the advent of improved large lesion technology including force-sensing catheters and the use of high power, although AE fistulae have also been observed with the use of low power along the left atrial posterior wall. Currently available discrete sensors probes, whether single or multiple, do not appear to significantly reduce injury rates. The purpose of this manuscript is to systematically review the incidence of esophageal thermal injury with and without LET monitoring and review the factors that may be associated with increased risk of injury.
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http://dx.doi.org/10.1016/j.tcm.2018.09.010DOI Listing
July 2019

New skip parameter to facilitate recurrence quantification of signals comprised of multiple components.

Chaos 2018 Aug;28(8):085718

Department of Cell and Molecular Physiology, Loyola University Chicago - Health Sciences Division, Maywood, Illinois 60153, USA.

Recurrence analyses are typically performed on discretized time series after applying proper embeddings, delays, and thresholds. In our study of atrial electrograms, we found limitations to this approach when sequential bipolar complexes were defined as the timings of the first two zero crosses following the initiation of each event. The reason for this is that each bipolar component consists of two points in odd-even pairings. Since recurrence analysis starts vectors on each sequential point, incorrect even-odd pairings occur for every other vector. To overcome this limitation, a new parameter SKIP is introduced such that recurrence vectors can skip 1 (or 2) points for signals with defined multiple components. To demonstrate the utility of parameter SKIP, we used the Courtemanche model to simulate the electrical activity in the human atrium on a square, two-dimensional plane with 800 × 800 nodes. Over this plane, a grid of 39 × 39 virtual unipoles was created. Neighboring unipoles formed 39 × 38 bipolar pairs, which were recorded as 1482 continuous and synchronous time series. At each unipolar site, the actual wavefront direction was determined by comparing the relative activation timings of the local intracellular potentials. Parameters were set such that the "tissue" exhibited both spiral waves (organized activity) and wave breakups (chaotic activity). For each bipolar complex in the continuous electrogram, discretized electrogram conformation was defined as the timing delays from the start of the complex to the first two zero-crosses. Long sequences of paired zero-cross timings were subjected to recurrence analysis using SKIP values of 0 (no skipping) and 1 (single skipping). Recurrence variables were computed and correlated with the absolute wavefront directions. The results showed that the introduction of the skipping window improved the correlations of some recurrence variables with absolute wavefront directions. This is critically important because such variables may be better markers for wavefront directions in human recordings when the absolute wavefront directions cannot be calculated directly.
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http://dx.doi.org/10.1063/1.5024845DOI Listing
August 2018

Ventricular Fibrillation Conversion Testing After Implantation of a Subcutaneous Implantable Cardioverter Defibrillator: Report From the National Cardiovascular Data Registry.

Circulation 2018 06 20;137(23):2463-2477. Epub 2018 Feb 20.

Division of Cardiology, Duke University Hospital, Durham, NC (D.J.F., S.M.A.-K.).

Background: Compared with transvenous implantable cardioverter defibrillators (ICDs), subcutaneous (S)-ICDs require a higher energy for effective defibrillation. Although ventricular fibrillation conversion testing (CT) is recommended after S-ICD implantation to ensure an adequate margin between the defibrillation threshold and maximum device output (80J), prior work found that adherence to this recommendation is declining.

Methods: We studied first-time recipients of S-ICDs (between September 28, 2012, and April 1, 2016) in the National Cardiovascular Database Registry ICD Registry to determine predictors of use of CT, predictors of an insufficient safety margin (ISM, defined as ventricular fibrillation conversion energy >65J) during testing, and inhospital outcomes associated with use of CT. Multivariable logistic regression analysis was used to predict use of CT and ISM. Inverse probability weighted logistic regression analysis was used to examine the association between use of CT and inhospital adverse events including death.

Results: CT testing was performed in 70.7% (n=5624) of 7960 patients with S-ICDs. Although deferral of CT was associated with several patient characteristics (including increased body mass index, increased body surface area, severely reduced ejection fraction, dialysis dependence, warfarin use, anemia, and hypertrophic cardiomyopathy), the facility effect was comparatively more important (area under the curve for patient level versus generalized linear mixed model: 0.619 versus 0.877). An ISM occurred in 6.9% (n=336) of 4864 patients without a prior ICD and was more common among white patients and those with ventricular pacing on the preimplant ECG, higher preimplant blood pressure, larger body surface area, higher body mass index, and lower ejection fraction. A risk score was able to identify patients at low (<5%), medium (5% to 10%), and high risk (>10%) for ISM. CT testing was not associated with a composite of inhospital complications including death.

Conclusions: Use of CT testing after S-ICD implantation was driven by facility preference to a greater extent than patient factors and was not associated with a composite of inhospital complications or death. ISM was relatively uncommon and is associated with several widely available patient characteristics. These data may inform ICD system selection and a targeted approach to CT.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988932PMC
June 2018

Postoperative Atrial Fibrillation and Maslow's Hammer.

Anesth Analg 2018 01;126(1):19-20

From the Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1213/ANE.0000000000002414DOI Listing
January 2018

Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes.

Cardiovasc Diabetol 2017 09 29;16(1):120. Epub 2017 Sep 29.

Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. Several risk factors promote AF, among which diabetes mellitus has emerged as one of the most important. The growing recognition that obesity, diabetes and AF are closely intertwined disorders has spurred major interest in uncovering their mechanistic links. In this article we provide an update on the growing evidence linking oxidative stress and inflammation to adverse atrial structural and electrical remodeling that leads to the onset and maintenance of AF in the diabetic heart. We then discuss several therapeutic strategies to improve atrial excitability by targeting pathways that control oxidative stress and inflammation.
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http://dx.doi.org/10.1186/s12933-017-0604-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622555PMC
September 2017

A method for quantifying recurrent patterns of local wavefront direction during atrial fibrillation.

Comput Biol Med 2017 10 1;89:497-504. Epub 2017 Sep 1.

The Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.

Introduction: Spiral wave reentry is a potential mechanism of atrial fibrillation (AF), but is difficult to differentiate clinically from multiple wavelet breakup using standard bipolar recordings. We developed a new methodology using bipolar recordings to estimate the direction of local activation wavefronts during AF by calculating the electrogram conformation (Egm-C). We subsequently used recurrence quantification analysis (RQA) of Egm-C to differentiate regions of spiral wave reentry from wavelet breakup.

Methods: A 2D computer simulation was created with regions containing a stable spiral wave and also regions of wavebreak. A grid of 40 × 40 unipolar electrodes was superimposed. At each site, the actual wavefront direction (WD) was determined by comparing relative activation timings of the local intracellular recordings, and the estimated wavefront direction (Egm-C) was determined from the morphology of the local bipolar electrogram. RQA of Egm-C was compared to RQA of actual WD in order to differentiate AF mechanisms.

Results: RQA of actual WD and Egm-C both distinguished regions of spiral wave reentry from wavelet breakup with high correlation between the two methods (recurrence rate, r = 0.96; determinism, r = 0.61; line max, r = 0.95; entropy, r = 0.84; p < 0.001 for all). In areas of stable spiral wave reentry, the recurrence plots of both Egm-C and actual WD demonstrated stable, periodic dynamics, while regions of wavelet breakup demonstrated chaotic behavior largely devoid of repetitive activation patterns.

Conclusion: Calculation of Egm-C allows RQA to be performed on bipolar electrograms during AF and differentiates regions of spiral wave reentry from multiple wavelet breakup.
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http://dx.doi.org/10.1016/j.compbiomed.2017.08.027DOI Listing
October 2017

Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter-defibrillators.

Med Devices (Auckl) 2017 16;10:165-188. Epub 2017 Aug 16.

Robert Wood Johnson Foundation Clinical Scholars Program, Yale School of Medicine.

Background: Machine learning methods may complement traditional analytic methods for medical device surveillance.

Methods And Results: Using data from the National Cardiovascular Data Registry for implantable cardioverter-defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%-20.9%; nonfatal ICD-related adverse events, 19.3%-26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%-37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, =0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, =-0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, =-0.042).

Conclusion: Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance.
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http://dx.doi.org/10.2147/MDER.S138158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566316PMC
August 2017

Arrhythmias after left ventricular assist device implantation: Incidence and management.

Trends Cardiovasc Med 2018 01 10;28(1):41-50. Epub 2017 Jul 10.

University of North Carolina-Division of Cardiology, Chapel Hill, NC.

The use of mechanical circulatory support has become an increasingly common practice in patients with heart failure, whether used as bridge to transplantation or as destination therapy. The last couple of decades has seen a drastic change in the functioning of the left ventricular assist devices (LVAD), changing from the first generation devices running on pulsatile flow to the current continuous flow devices. Atrial and ventricular arrhythmias are common among heart failure patients, and though the systematic circulation is well supported in patients on mechanical circulatory support, these arrhythmias can still be the cause of detrimental symptoms and lead to potentially fatal outcomes. Several studies have shown that mortality rates in LVAD recipients secondary to lethal arrhythmias are uncommon, and newer generation continuous flow devices particularly seem to support hemodynamic support well. While it is common practice to implant ICDs in patients with LVADs and a history of ventricular arrhythmias, the efficacy behind this practice at preventing sudden death in this population is unknown. In this review, we highlight what is already known about the complications, management and treatment of atrial and ventricular arrhythmias in patients with LVAD devices.
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http://dx.doi.org/10.1016/j.tcm.2017.07.002DOI Listing
January 2018

Addition of Blood Pressure and Weight Transmissions to Standard Remote Monitoring of Implantable Defibrillators and its Association with Mortality and Rehospitalization.

Circ Cardiovasc Qual Outcomes 2017 05;10(5)

From the Department of Medicine, Shawnee Mission Medical Center, Shawnee Mission, KS (M.O.A.-C.); Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine and Center of Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT (H.B., J.P.C., J.G.A.); Boston Scientific Corporation, St. Paul, MN (P.W.J., K.M.S.); Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (L.M., P.D.V., F.A.M.); and VA Eastern Colorado Health Care System, Denver (P.D.V.).

Background: Among patients with implantable defibrillators (ICD), use of remote patient monitoring (RPM) is associated with lower risk of death and rehospitalization. Standard ICD RPM can be supplemented with weight and blood pressure data. It is not known whether standard RPM plus routine weight and blood pressure transmission (RPM+) is associated with better outcomes.

Methods And Results: RPM+ patients (n=4106) were compared with patients who only transmitted standard ICD RPM data (n=14 183). Logistic regression models identified patient, physician, and hospital characteristics associated with RPM+ utilization. Mortality and rehospitalization were examined using landmark analyses at 180 days after ICD implant in Medicare fee-for-service patients. In these analyses, we examined the independent association between RPM+ utilization and times to events up to 3 years after device implantation with Cox regression models. We further examined whether the association between RPM+ and outcomes varied by frequency or type of transmissions. Determinants of RPM+ utilization included impaired ejection fraction, cardiac resynchronization therapy, and institutional practice. The risk of mortality of RPM+ patients was similar to standard ICD RPM patients (hazard ratio, 1.06; 95% confidence interval, 0.94-1.19; =0.34). RPM+ patients also had similar risks of all-cause hospitalization (subdistribution hazard ratio, 1.03; 95% confidence interval, 0.94-1.14; =0.52), cardiovascular hospitalization (subdistribution hazard ratio, 0.92; 95% confidence interval, 0.83-1.02; =0.15), or heart failure hospitalizations (subdistribution hazard ratio, 0.90; 95% confidence interval, 0.78-1.05; =0.18). RPM+ transmission frequency was not associated with outcomes.

Conclusions: In patients using standard ICD RPM, the added transmission of weight and blood pressure data was not associated with improved outcomes.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.116.003087DOI Listing
May 2017

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults.

Circ Cardiovasc Genet 2017 Feb;10(1)

From the Division of Cardiovascular Medicine (S.B.S., E.S., L.S., M.D.A.Z., B.A., J.G.A., M.M., D.J., A.M.), Yale Program for Cardiovascular Genetics (S.B.S., E.S., L.S., F.H.-S., A.M.), Department of Genetics, Yale School of Medicine, New Haven, CT (D.D., A.E.B., R.P.L., A.M.); Division of Cardiovascular Medicine, Department of Radiology (S.B.S.) and Division of Cardiac Imaging (S.B.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Key Laboratory of Clinical Trail Research in Cardiovascular Drugs, Ministry of Health Cardiovascular Institute, Fu Wai Hospital, CAMS and PUMC, Beijing, China (Y.J.).

Background: With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The use of whole exome sequencing for clinical diagnosis, risk stratification, and management of inherited CVD has not been previously evaluated.

Methods And Results: We analyzed the results of whole exome sequencing in first 200 adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics. Genetic diagnosis was reached and reported with a success rate of 26.5% (53 of 200 patients). This compares to 18% (36 of 200) that would have been diagnosed using commercially available genetic panels (P=0.04). Whole exome sequencing was particularly useful for clinical diagnosis in patients with aborted sudden cardiac death, in whom the primary insult for the presence of both depressed cardiac function and prolonged QT had remained unknown. The analysis of the remaining cases using genome annotation and disease segregation led to the discovery of novel candidate genes in another 14% of the cases.

Conclusions: Whole exome sequencing is an exceptionally valuable screening tool for its capability to establish the clinical diagnosis of inherited CVDs, particularly for poorly defined cases of sudden cardiac death. By presenting novel candidate genes and their potential disease associations, we also provide evidence for the use of this genetic tool for the identification of novel CVD genes. Creation and sharing of exome databases across centers of care should facilitate the discovery of unknown CVD genes.
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http://dx.doi.org/10.1161/CIRCGENETICS.116.001573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5245580PMC
February 2017

Editorial commentary: Virtual medicine-A better reality?

Trends Cardiovasc Med 2016 11 2;26(8):731-732. Epub 2016 Jul 2.

Division of Cardiology, University of North Carolina, Chapel Hill, NC.

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http://dx.doi.org/10.1016/j.tcm.2016.06.012DOI Listing
November 2016

Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT).

Am J Cardiol 2016 Dec 31;118(11):1680-1684. Epub 2016 Aug 31.

The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, New York; The Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Medical Center, New York, New York.

Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TTR) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TTR scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TTR scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TTR score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TTR score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TTR scores were associated with better TTR.
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http://dx.doi.org/10.1016/j.amjcard.2016.08.047DOI Listing
December 2016

A Fresh Perspective on Atrial Fibrillation.

J Am Coll Cardiol 2016 08;68(9):905-7

Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut.

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http://dx.doi.org/10.1016/j.jacc.2016.06.019DOI Listing
August 2016

Long-Term Risk for Device-Related Complications and Reoperations After Implantable Cardioverter-Defibrillator Implantation: An Observational Cohort Study.

Ann Intern Med 2016 Jul 3;165(1):20-29. Epub 2016 May 3.

Background: Long-term nonfatal outcomes after implantable cardioverter-defibrillator (ICD) placement are poorly defined.

Objective: To determine the long-term risk for ICD-related complications requiring reoperation or hospitalization and reoperation for reasons other than complications, and to assess associated patient and device characteristics.

Design: Observational cohort study of ICD implantations from the National Cardiovascular Data Registry ICD registry linked with Medicare fee-for-service claims data.

Setting: 1437 U.S. hospitals.

Patients: 114 484 patients aged 65 years or older (mean, 74.8 years [SD, 6.2]; 72.4% male) receiving an ICD for the first time from 2006 to 2010 (single-chamber, 19.8%; dual-chamber, 41.3%; cardiac resynchronization therapy with a defibrillator [CRT-D], 38.9%).

Measurements: Rate and cumulative incidence of ICD-related complications requiring reoperation or hospitalization and reoperation for reasons other than complications.

Results: During a median follow-up of 2.7 years (interquartile range, 1.8 to 3.9 years), 40 072 patients died, representing 12.6 (95% CI, 12.5 to 12.7) deaths per 100 patient-years of follow-up. When the risk for death was accounted for, there were 6.1 (CI, 6.0 to 6.2) ICD-related complications per 100 patient-years that required reoperation or hospitalization and 3.9 (CI, 3.8 to 4.0) reoperations per 100 patient-years for reasons other than complications. Overall, 10 patients had complications or reoperation per 100 patient-years of follow-up. Younger age at implantation (65 to 69 vs. >85 years) (hazard ratio [HR], 1.55 [CI, 1.43 to 1.69]), receipt of a CRT-D device (HR, 1.38 [CI, 1.31 to 1.45]) versus a single-chamber device, female sex (HR, 1.16 [CI, 1.12 to 1.21]), and black race (HR, 1.14 [CI, 1.05 to 1.23]) were associated with the greatest increased risks for ICD-related complications.

Limitation: The analysis was limited to Medicare fee-for-service patients aged 65 years or older.

Conclusion: Patients have a high rate of device-related complications and reoperation for other causes after ICD implantation. Risks of ICD implantation and strategies to reduce them should be actively considered before implantation.

Primary Funding Source: American College of Cardiology Foundation's National Cardiovascular Data Registry.
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http://dx.doi.org/10.7326/M15-2732DOI Listing
July 2016