Publications by authors named "Timothy M Markman"

28 Publications

  • Page 1 of 1

Racial/Ethnic and Socioeconomic Disparities in Management of Incident Paroxysmal Atrial Fibrillation.

JAMA Netw Open 2021 02 1;4(2):e210247. Epub 2021 Feb 1.

Cardiovascular Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Importance: In patients with paroxysmal atrial fibrillation (AF), rhythm control with either antiarrhythmic drugs (AADs) or catheter ablation has been associated with decreased symptoms, prevention of adverse remodeling, and improved cardiovascular outcomes. Adoption of advanced cardiovascular therapeutics, however, is often slower among patients from racial/ethnic minority groups and those with lower income.

Objective: To ascertain the cumulative rates of AAD and catheter ablation use for the management of paroxysmal AF and to investigate for the presence of inequities in AF management by evaluating the association of race/ethnicity and socioeconomic status with their use in the United States.

Design, Setting, And Participants: This cohort study obtained inpatient, outpatient, and pharmacy claims data from the Optum Clinformatics Data Mart between October 1, 2015, and June 30, 2019. Adult patients (aged ≥18 years) in the database with a diagnosis of incident paroxysmal AF were identified. Patients were excluded if they did not have continuous insurance enrollment for at least 1 year before and at least 6 months after study entry.

Exposures: Race/ethnicity and zip code-linked median household income.

Main Outcomes And Measures: Treatment with a rhythm control strategy, and catheter ablation specifically, among those who received rhythm control. Multivariable logistic regression models were used to assess the association of race/ethnicity and zip code-linked median household income with a rhythm control strategy (AADs or catheter ablation) vs a rate control strategy as well as with catheter ablation vs AADs among those receiving rhythm control.

Results: Of the 109 221 patients who met the inclusion criteria, 55 185 were men (50.5%) and 73 523 were White (67.3%), with a median (interquartile range) age of 75 (68-82) years. A total of 86 359 patients (79.1%) were treated with rate control, 19 362 patients (17.7%) with AADs, and 3500 (3.2%) with catheter ablation. Between 2016 and 2019, the cumulative percentage of patients treated with catheter ablation increased from 1.6% to 3.8%. In multivariable analyses, Black race (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94; P < .001) and lower zip code-linked median household income (aOR for <$50 000: 0.83 [95% CI, 0.79-0.87; P < .001]; aOR for $50 000-$99 999: 0.92 [95% CI, 0.88-0.96; P = <.001] compared with ≥$100 000) were independently associated with lower use of rhythm control. Latinx ethnicity (aOR, 0.73; 95% CI, 0.60-0.89; P = .002) and lower zip code-linked median household income (aOR for <$50 000: 0.61 [95% CI, 0.54-0.69; P < .001]; aOR for $50 000-$99 999: 0.81 [95% CI, 0.72-0.90; P < .001] compared with ≥$100 000) were independently associated with lower catheter ablation use among those receiving rhythm control.

Conclusions And Relevance: This study found that despite increased use of rhythm control strategies for treatment of paroxysmal AF, catheter ablation use remained low and patients from racial/ethnic minority groups and those with lower income were less likely to receive rhythm control treatment, especially catheter ablation. These findings highlight inequities in paroxysmal AF management based on race/ethnicity and socioeconomic status.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910819PMC
February 2021

Catheter ablation of atrial fibrillation: cardiac imaging guidance as an adjunct to the electrophysiological guided approach.

Europace 2021 Apr;23(4):520-528

Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Founders 9118, Philadelphia, PA, USA.

Catheter ablation is increasingly utilized to treat patients with atrial fibrillation (AF). Despite progress in technology and procedural strategy, there remain significant limitations with suboptimal outcomes. The role of imaging has continued to evolve, and multimodality imaging now presents an important opportunity to make substantial progress in the safety and efficacy of ablation. In this review, we discuss the history of imaging in the ablation of AF with a specific focus on the ability of cardiac computed tomography and magnetic resonance imaging to characterize anatomy, arrhythmogenic substrate, and guide ablation strategy. We will review the progress that has been made and highlight many of the limitations as well as future directions for the field.
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http://dx.doi.org/10.1093/europace/euaa249DOI Listing
April 2021

Improvement in tricuspid regurgitation following catheter ablation of atrial fibrillation.

J Cardiovasc Electrophysiol 2020 11 14;31(11):2883-2888. Epub 2020 Aug 14.

Cardiovascular Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: Functional tricuspid regurgitation (TR) remains a challenging clinical problem with poor outcomes and few effective treatments. Atrial fibrillation (AF) has been associated with functional TR. We sought to determine whether restoring sinus rhythm through catheter ablation of AF can decrease the degree of TR.

Methods And Results: A retrospective cohort study of patients undergoing AF ablation between 2011 and 2017 at a single center was conducted. We included patients with at least moderate TR on echocardiogram within the year preceding ablation, who underwent repeat echocardiogram within the year following ablation. Formal quantitative analysis was performed by an experienced research echocardiographer, blinded to arrhythmia outcomes. Arrhythmia-free survival was correlated to the extent of improvement in TR. Thirty-six patients met the inclusion criteria. A baseline echocardiogram was performed 37 ± 68 days before ablation and follow-up echocardiogram 139 ± 112 days following ablation. Patients were 63.7 ± 11.1 years old with a mean CHA DS -VASc score of 2.7 ± 1.7. The degree of TR improved by at least one grade in 23 patients (64%). TR area decreased from 11.6 ± 3.4 to 7.0 ± 3.5 cm (p < .001) following ablation. Freedom from AF postablation was associated with a greater likelihood of improvement in TR by at least one grade (100% vs. 41%, p = .02).

Conclusions: In patients with AF and at least moderate TR, catheter ablation is associated with substantial improvement in TR severity.
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http://dx.doi.org/10.1111/jce.14707DOI Listing
November 2020

Mapping Endocardial-Epicardial Dissociation: Significance for Atrial Fibrillation Ablation.

JACC Clin Electrophysiol 2020 07;6(7):846-848

Section for Cardiac Electrophysiology, Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1016/j.jacep.2020.04.026DOI Listing
July 2020

Durability of posterior wall isolation after catheter ablation among patients with recurrent atrial fibrillation.

Heart Rhythm 2020 10 7;17(10):1740-1744. Epub 2020 May 7.

Department of Medicine, Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Electrical posterior wall isolation (PWI) is increasingly being used for the treatment of patients with atrial fibrillation (AF). Few data exist on the durability of PWI using current technology.

Objective: The purpose of this study was to characterize the frequency and location of posterior wall reconnection at the time of repeat catheter ablation for AF.

Methods: We performed a single-center retrospective cohort study of 50 patients undergoing repeat AF ablation after previous PWI. Durability of PWI was assessed at the time of repeat ablation based on posterior wall entrance and exit block. Sites of posterior wall reconnection were characterized based on review of recorded electrical signals and electroanatomic maps.

Results: At the time of repeat ablation, mean age was 67 ± 10 years, 31 of 50 patients had persistent AF, and mean CHADS-VASc score was 3.0 ± 1.8. Of the 50 patients, 30 had durable PWI at repeat ablation, 1.4 ± 1.6 years after the index procedure. Patients with posterior wall reconnection required repeat ablation earlier (0.9 ± 0.6 years vs1.8 ± 1.9 years from index PWI; P = .048) and were more likely to have atypical atrial flutter (55% vs 27%; P = .043). Among patients with posterior wall reconnection, the roof was the most common site of reconnection (14/20), and 12 patients had multiple regions of reconnection noted.

Conclusion: Posterior wall reconnection is noted in 40% of patients undergoing repeat ablation after an index PWI. The roof of the left atrium is the most common site of posterior wall reconnection.
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http://dx.doi.org/10.1016/j.hrthm.2020.05.005DOI Listing
October 2020

Moving Toward Improved Risk Stratification in Patients With Dilated Cardiomyopathy.

Circ Cardiovasc Imaging 2020 04 21;13(4):e010629. Epub 2020 Apr 21.

Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1161/CIRCIMAGING.120.010629DOI Listing
April 2020

Trends in Antiarrhythmic Drug Use Among Patients in the United States Between 2004 and 2016.

Circulation 2020 03 16;141(11):937-939. Epub 2020 Mar 16.

Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044109DOI Listing
March 2020

Characterization of Structural Changes in Arrhythmogenic Right Ventricular Cardiomyopathy With Recurrent Ventricular Tachycardia After Ablation: Insights From Repeat Electroanatomic Voltage Mapping.

Circ Arrhythm Electrophysiol 2020 01 10;13(1):e007611. Epub 2020 Jan 10.

Electrophysiology Section, Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia.

Background: Data characterizing structural changes of arrhythmogenic right ventricular (RV) cardiomyopathy are limited.

Methods: Patients presenting with left bundle branch block ventricular tachycardia in the setting of arrhythmogenic RV cardiomyopathy with procedures separated by at least 9 months were included.

Results: Nineteen consecutive patients (84% males; mean age 39±15 years [range, 20-76 years]) were included. All 19 patients underwent 2 detailed sinus rhythm electroanatomic endocardial voltage maps (average 385±177 points per map; range, 93-847 points). Time interval between the initial and repeat ablation procedures was mean 50±37 months (range, 9-162). No significant progression of voltage was observed (bipolar: 38 cm [interquartile range (IQR), 25-54] versus 53 cm [IQR, 25-65], =0.09; unipolar: 116 cm [IQR, 61-209] versus 159 cm [IQR, 73-204], =0.36) for the entire study group. There was a significant increase in RV volumes (percentage increase, 28%; 206 mL [IQR, 170-253] versus 263 mL [IQR, 204-294], <0.001) for the entire study population. Larger scars at baseline but not changes over time were associated with a significant increase in RV volume (bipolar: Spearman ρ, 0.6965, =0.006; unipolar: Spearman ρ, 0.5743, =0.03). Most patients with progressive RV dilatation (8/14, 57%) had moderate (2 patients) or severe (6 patients) tricuspid regurgitation recorded at either initial or repeat ablation procedure.

Conclusions: In patients with arrhythmogenic RV cardiomyopathy presenting with recurrent ventricular tachycardia, >10% increase in RV endocardial surface area of bipolar voltage consistent with scar is uncommon during the intermediate term. Most recurrent ventricular tachycardias are localized to regions of prior defined scar. Voltage indexed scar area at baseline but not changes in scar over time is associated with progressive increase in RV size and is consistent with adverse remodeling but not scar progression. Marked tricuspid regurgitation is frequently present in patients with arrhythmogenic RV cardiomyopathy who have progressive RV dilation.
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http://dx.doi.org/10.1161/CIRCEP.119.007611DOI Listing
January 2020

Baseline ST elevation and myocardial scar: Results from the multi-ethnic study of atherosclerosis.

J Electrocardiol 2019 Sep - Oct;56:29-33. Epub 2019 Jun 18.

Department of Medicine, The Johns Hopkins University, Baltimore, MD, United States of America; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Division of Cardiology, Section for Cardiac Electrophysiology, The Johns Hopkins University, Baltimore, MD, United States of America; Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States of America.

Background: The mechanism of ST elevation on baseline electrocardiograms (ECG) unknown but it may be associated with abnormal myocardial substrate. This paper evaluates whether clinically unrecognized myocardial scar on cardiac magnetic resonance imaging (CMR) is associated with ST elevation at baseline.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease at enrollment in 2000-2002. Our cohort included 1365 participants who underwent both ECG and contrast enhanced CMR in the 5th examination (2010-2012). Multivariable logistic regression examined the association of ST elevation and CMR defined regional myocardial scar after adjusting for cardiovascular risk factors.

Results: Of 1365 participants (58 ±9 years, 52% men), 105 (8%) had scar on CMR. Of these, the scar in 40 participants followed an ischemic pattern and in the other 65 participants followed a non-ischemic pattern. ST elevation at the 5th examination was present in 435 participants: 40 (0.9%) had ST elevations in inferior and 427 (98%) in lateral leads. 2/40 (5%) and 22/427 (5%) participants with inferior and lateral ST elevations, respectively, had evidence of scar. 15 (1.0%) had myocardial scar noted in the basal anterior region. In the fully adjusted models, ST elevation was associated with scar in basal anterior region (OR 18.2, p = 0.031).

Conclusions: In a community population, ST elevation at baseline in the inferior or lateral leads was associated with myocardial scar in the basal inferior and anterior segments. The previously described association between ST elevation and increased mortality may be mediated by myocardial scar.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744967PMC
June 2021

Clinical and electrophysiological characteristics of idiopathic ventricular arrhythmias originating from the slow pathway region.

Heart Rhythm 2019 09 18;16(9):1421-1428. Epub 2019 Jun 18.

Division of Cardiology, Electrophysiology Section, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: The slow pathway region (SPR) is commonly targeted during ablation of atrioventricular nodal reentrant tachycardia. However, its role in idiopathic ventricular arrhythmias (IVAs) remains unknown.

Objective: The purpose of this study was to describe the electrocardiographic and electrophysiological characteristics of IVAs that were successfully ablated from the SPR.

Methods: Medical records of consecutive patients undergoing ablation of IVAs in the para-Hisian region between 2010 and 2018 were reviewed to identify subjects whose ventricular arrhythmias were targeted from the SPR.

Results: Among 63 patients with para-Hisian IVAs undergoing ablation, the SPR was targeted in 12 (20%; mean age 64 ± 7 years; 9 men). All patients presented with ventricular premature depolarizations manifesting left bundle branch block morphology with variable precordial transition (leads V-V) and a mean QRS duration of 131 ± 11 ms. In all cases, leads I and aVL had positive forces (R or Rs) and lead aVR had negative forces (QS or Qr). In the majority of cases, lead II had positive forces (R or Rs; n = 9 [75%]) and lead III had negative forces (rS or QS; n = 9 [75%]). Mean activation at the SPR was 31 ± 5 ms pre-QRS. All patients had initial ablation with radiofrequency, resulting in junctional rhythm in 9 (75%); 3 (25%) patients required additional cryoablation. Ablation was successful in 11 patients (92%). One patient required a permanent pacemaker for heart block but subsequently recovered intrinsic conduction.

Conclusion: The SPR can be a source of IVAs, which can be safely and successfully ablated in most cases using radiofrequency energy. IVAs arising from this location manifest unique electrocardiographic features.
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http://dx.doi.org/10.1016/j.hrthm.2019.06.013DOI Listing
September 2019

Cardio-oncology: management of cardiovascular toxicity.

F1000Res 2019 30;8. Epub 2019 Jan 30.

Cancer Treatment Centers of America at Eastern Regional Medical Center, Philadelphia, PA, USA.

Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring. In the second of this two-part review series, we focus on the management of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.
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http://dx.doi.org/10.12688/f1000research.14542.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354320PMC
June 2020

Magnetic Resonance Imaging as the Arbitrator of Optimal Lesion Delivery During Catheter Ablation.

JACC Clin Electrophysiol 2018 12;4(12):1595-1597

Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.jacep.2018.08.020DOI Listing
December 2018

Treatment of ventricular arrhythmias: What's New?

Trends Cardiovasc Med 2019 07 22;29(5):249-261. Epub 2018 Sep 22.

Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, United States.

Ventricular arrhythmias can present as asymptomatic premature ventricular complexes (PVCs) or non-sustained ventricular tachycardia (VT), symptomatic presentation of the former arrhythmias, or sustained VT with minimal symptoms to full hemodynamic collapse. The most important and feared consequence of VT is sudden cardiac death (SCD). Independent of SCD risk, frequent ventricular arrhythmias can cause substantial symptoms. Implantable cardioverter defibrillators (ICDs) are the foundation of managing patients at high risk for SCD due to their ability to automatically identify and defibrillate malignant ventricular arrhythmias. Unfortunately, defibrillation is associated with significant physical and emotional adverse effects. Other treatment options include antiarrhythmic drugs, which have substantial toxicities and limited efficacy, and catheter ablation. The techniques and strategies for VT ablation have advanced considerably in recent years leading to a rapid expansion of indications and use. In this review, we discuss current state of the art therapies for ventricular arrhythmias and highlight some of the most promising areas of ongoing development.
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http://dx.doi.org/10.1016/j.tcm.2018.09.014DOI Listing
July 2019

Catheter ablation versus conventional treatment of atrial fibrillation in patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials.

J Interv Card Electrophysiol 2018 Oct 31;53(1):19-29. Epub 2018 Jul 31.

Electrophysiology Section, Cardiovascular Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: To evaluate whether catheter ablation is superior to conventional therapy for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF).

Methods: Electronic databases were searched for randomized, controlled trials of AF ablation compared with conventional therapy in adults with AF and HFrEF. Odds ratio (OR), standard mean difference (SMD), and 95% confidence intervals (CIs) were measured using the Mantel-Haenszel method.

Results: There were seven trials including 856 patients (mean age 62 years, male 86%). All-cause mortality in patients who underwent ablation was 10% vs. 19% in those who received conventional treatment (four trials, 668 patients, 47% relative reduction, 9% absolute reduction; OR 0.46, 95% CI 0.29-0.72). Improvement in the left ventricular ejection fraction was significantly higher for patients undergoing ablation (+ 9 ± 10%) compared to conventional treatment (+ 2 ± 7%) (seven trials, 856 patients, SMD 0.68, 95% CI 0.28-1.08). Freedom from AF was higher in patients undergoing ablation (seven trials, 856 patients, 70% vs. 18%, respectively; 64% relative reduction, 52% absolute reduction; OR 0.03 95% CI 0.01-0.11). There was no significant difference in major complications between both strategies (OR 1.13, 95% CI 0.58-2.20).

Conclusions: Catheter ablation for AF in patients with HFrEF decreases mortality and AF recurrence and improves left ventricular function, functional capacity, and quality of life, when compared to conventional management, without increasing complications.
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http://dx.doi.org/10.1007/s10840-018-0425-0DOI Listing
October 2018

Update on MRI Safety in Patients with Cardiac Implantable Electronic Devices.

Radiology 2018 Sep 3;288(3):656-657. Epub 2018 Jul 3.

From the Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Founders 9118, Philadelphia, PA 19104 (T.M.M., S.N.); Division of Cardiology, Section for Cardiac Electrophysiology (H.R.H., S.N.), and Departments of Radiology and Biomedical Engineering (H.R.H.), The Johns Hopkins University, Baltimore, Md.

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http://dx.doi.org/10.1148/radiol.2018180360DOI Listing
September 2018

Cardio-Oncology: mechanisms of cardiovascular toxicity.

F1000Res 2018 25;7:113. Epub 2018 Jan 25.

Cancer Treatment Centers of America at Eastern Regional Medical Center, Philadelphia, Pennsylvania, USA.

The therapeutic options available to treat a wide range of malignancies are rapidly increasing. At the same time, the population being treated is aging with more cardiovascular risk factors, comorbid conditions, and associated poor cardiac reserve. Both traditional chemotherapeutic agents (for example, anthracyclines) and newer therapies (for example, targeted tyrosine kinase inhibitors and immune checkpoint inhibitors) have demonstrated profound cardiovascular toxicities. It is important to understand the mechanisms of these toxicities to establish strategies for the prevention and management of complications-arrhythmias, heart failure, and even death. In the first of this two-part review series, we focus on what is known and hypothesized about the mechanisms of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.
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http://dx.doi.org/10.12688/f1000research.12598.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785712PMC
January 2018

Cardiac Magnetic Resonance for Lesion Assessment in the Electrophysiology Laboratory.

Circ Arrhythm Electrophysiol 2017 11;10(11)

From the Division of Cardiology (T.M.M., S.N.) and Section for Cardiac Electrophysiology (S.N.), Hospital of the University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1161/CIRCEP.117.005839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687838PMC
November 2017

Case of Ovarian Cancer in a Woman with Undiagnosed Graves' Disease: A Case Report and Review of the Literature.

Case Rep Oncol 2017 May-Aug;10(2):452-454. Epub 2017 May 23.

Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.

Epithelial ovarian cancer (OC) is a leading cause of death among females in the United States, due in part to challenges of diagnosis in the early stages of the disease. While efforts are underway to develop a high-quality screening test, it is equally important to consider whether high-risk populations are appropriate to screen. One such population may be females with hyperthyroidism, as epidemiologic studies have shown an association between this condition and OC. In this report, we present a case of a female with OC and Graves' disease to highlight the potential significance of this association.
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http://dx.doi.org/10.1159/000475807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471773PMC
May 2017

Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy.

Pediatr Blood Cancer 2017 Nov 28;64(11). Epub 2017 Apr 28.

Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.

Background: Anthracycline use is limited by cardiotoxicity, including arrhythmias and left ventricular (LV) dysfunction. We aim to characterize the association between electrophysiological changes and LV dysfunction.

Methods: A retrospective chart review was conducted, including all 147 pediatric cancer survivors at our institution over 18 years of age and treated with an anthracycline. One hundred thirty-four patients who had at least one electrocardiogram (ECG) and echocardiogram were analyzed. The association between dysfunction and baseline characteristics, treatment history, and electrocardigraphic parameters were analyzed using multivariable logistic regression. Additionally, a longitudinal generalized estimating equation (GEE) model was used to examine the temporal association between repeated measure corrected QT (QTc) intervals and subsequent LV function.

Results: In our population, 24% of patients had LV dysfunction. The initial posttreatment QTc interval was longer in patients with LV dysfunction (438 ± 35 vs. 420 ± 20 msec, P = 0.002). In logistic regression analysis, QTc interval (P < 0.001) and cumulative radiation dose (P = 0.027) were associated with LV dysfunction. On ECGs performed prior to evidence of LV dysfunction, the QTc was longer than on ECGs preceding a normal echocardiogram (451 ± 32 msec vs. 423 ± 25 msec, P < 0.001). Mean time from QTc ≥ 450 msec to evidence of LV dysfunction was 1.8 ± 2.9 years. In the longitudinal GEE model, QTc prolongation was associated with subsequent decreased fractional shortening.

Conclusions: Among adult survivors of pediatric cancer treated with anthracyclines, prolongation of the QTc interval was associated with subsequent LV dysfunction.
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http://dx.doi.org/10.1002/pbc.26556DOI Listing
November 2017

Risk Stratification for Sudden Cardiac Death: Is It Too Late to Establish a Role for Cardiac MRI?

Circulation 2017 05 28;135(22):2116-2118. Epub 2017 Mar 28.

From Department of Medicine, The Johns Hopkins University, Baltimore, MD (T.M.M.); and Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia (S.N.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.027958DOI Listing
May 2017

Association of left atrial structure and function and incident cardiovascular disease in patients with diabetes mellitus: results from multi-ethnic study of atherosclerosis (MESA).

Eur Heart J Cardiovasc Imaging 2017 Oct;18(10):1138-1144

Department of Medicine, The Johns Hopkins University, 600 North Wolfe Street, MD 21287, Baltimore, USA.

Aims: Diabetes mellitus (DM) is associated with the development of cardiovascular disease (CVD). Morphological changes in the left atrium (LA) may appear before symptoms. We aimed to investigate the association between cardiac magnetic resonance imaging (CMR) measured LA structure and function and incident CVD in asymptomatic individuals with DM.

Methods And Results: Tissue tracking CMR was used to measure LA size and phasic function (emptying fractions and strain) on all 536 Multi-Ethnic Study of Atherosclerosis (MESA) participants with DM and available CMR at baseline in 2000-2002. At the time of enrolment, all participants were free of clinically recognized CVD, which was defined as MI, resuscitated cardiac arrest, angina, stroke, heart failure, and atrial fibrillation. Cox regression was used to assess the association of LA parameters with incident CVD adjusted for traditional cardiovascular risk factors, LV mass, NT Pro-BNP and maximum LA volume. Kaplan-Meier curves, adjusted for traditional risk factors, were generated for each LA measurement for the 25% of participants with the most abnormal values versus the remaining 75%. After a mean follow up of 11.4 ± 3.4 years, 141 individuals developed CVD. Individuals with incident CVD (mean age 66 years, 66% male vs. mean age 64 years, 50% male) had larger maximum and minimum LA volume index (LAVI) (32.1 vs. 26.8 mm3/m2; 19.4 vs. 14.2 mm3/m2 respectively, P < 0.001 for both), and lower total, passive, and active EF than those without CVD (P < 0.01 for all). In the fully adjusted model, there was a significant association of minimum LAVI, LA total EF, LA passive EF and LA active EF with incident CVD (HR 1.12 per mm3/m2, P < 0.001; HR 0.95 per %, P < 0.001; HR 0.97 per %, P = 0.021; HR 0.98 per %, P < 0.027, respectively).

Conclusions: CMR measured LA minimum volume and LA function as measured by emptying fraction are predictive of CVD in a diabetic multi-ethnic population free of any clinically recognized CVD at baseline.
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http://dx.doi.org/10.1093/ehjci/jew332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837690PMC
October 2017

Anticoagulation for atrial fibrillation in dialysis patients: What is known and what does the future hold?

Heart Rhythm 2017 05 20;14(5):652-653. Epub 2017 Feb 20.

Division of Cardiology, Section for Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2017.02.019DOI Listing
May 2017

Arrhythmia and Electrophysiological Effects of Chemotherapy: A Review.

Oncology 2016 4;91(2):61-8. Epub 2016 Jun 4.

Department of Medicine, The Johns Hopkins University, Baltimore, Md., USA.

Importance: Cardiotoxicity is an important limiting factor in the use of antineoplastic agents. The risk of arrhythmia and the electrophysiological effects of these agents are poorly characterized though increasing evidence suggests a high prevalence of complications.

Observations: Patients with substantial cardiovascular risk factors are often excluded from clinical trials, while the aging population of patients actually receiving therapies may have an underlying arrhythmogenic substrate due to comorbidities. Risk stratification of patients before the selection of a therapeutic regimen is essential. Given the regular use of combination therapies, the potential for arrhythmia of each agent must be fully understood. Despite limited data and understanding in clinical practice, decisions on whether to initiate specific therapies in high-risk patients and how to manage the associated complications are made regularly.

Conclusions And Relevance: This review describes the observed arrhythmias and proposed mechanisms for several major classes of antineoplastic agents. It also provides recommendations for risk stratification, monitoring, prophylaxis, and therapy, emphasizing the need for a collaborative relationship between oncologists and cardiologists and areas for future research.
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http://dx.doi.org/10.1159/000446374DOI Listing
January 2017

Cardiotoxicity of antineoplastic agents: what is the present and future role for imaging?

Curr Oncol Rep 2014 ;16(8):396

As antineoplastic treatment options expand at an increasing rate, both traditional and novel agents continue to be limited by their cardiotoxic effects. While functional decline becomes clinically apparent at late states of toxicity, little is known about early stages during which treatment or prevention may still be an option. Several imaging modalities,including echocardiography, multiple gated acquisition, and cardiac magnetic resonance imaging have the ability to identify cardiac effects before they produce clinical symptoms.Here we discuss the current and future role of cardiac imaging in the assessment of cardiotoxicity of antineoplastic agents. effects on cardiac tissue, resulting in myocardial cellular damage,and ultimately lead to a wide range of effects including electrophysiological abnormalities, symptomatic heart failure(HF), and even death. This represents a limiting factor in the therapy of several otherwise treatable neoplasms [2].The cardiotoxicity of antineoplastic agents raises several important questions regarding the actual prevalence of cardiac toxicity, the ability to effectively treat or prevent such effects with pharmaceutical interventions, and the availability of a means for early diagnosis. Here, we focus on the latter, specifically examining current and potential future imaging strategies to detect the cardiac effects of chemotherapeutic agents.
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http://dx.doi.org/10.1007/s11912-014-0396-yDOI Listing
January 2015

Language development after cochlear implantation: an epigenetic model.

J Neurodev Disord 2011 Dec 19;3(4):388-404. Epub 2011 Nov 19.

Johns Hopkins School of Medicine, Baltimore, MD, USA.

Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic-phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent-child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child's acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience.
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http://dx.doi.org/10.1007/s11689-011-9098-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230757PMC
December 2011
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