126 results on '"Tisdale JE"'
Search Results
2. Influence of oral progesterone on drug-induced QT interval lengthening, JACC Clin EP 2016.pdf
- Author
-
Tisdale JE, Jaynes HA, Overholser BR, Sowinski KM, Flockhart DA, and Kovacs RJ
- Subjects
FOS: Clinical medicine ,110201 Cardiology (incl. Cardiovascular Diseases) - Abstract
Published journal article describing the results of this work
- Published
- 2018
- Full Text
- View/download PDF
3. Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: a prospective, observational study in a large urban academic medical center in the US.
- Author
-
Tisdale JE, Wroblewski HA, Overholser BR, Kingery JR, Trujillo TN, Kovacs RJ, Tisdale, James E, Wroblewski, Heather A, Overholser, Brian R, Kingery, Joanna R, Trujillo, Tate N, and Kovacs, Richard J
- Abstract
Background: Cardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation.Objective: The aim of this study was to determine the prevalence of Bazett's-corrected QT (QT(c)) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QT(c) interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization.Methods: This was a prospective, observational study conducted over a 1-year period (October 2008-October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as 'outpatient' in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QT(c) interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QT(c) interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there were published data indicating that the drug causes QT interval prolongation and/or TdP. Study endpoints were (i) prevalence of QT(c) interval prolongation upon admission to the Cardiac Medical Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion of patients admitted to the CMCCU/AHCU with QT(c) interval prolongation who subsequently were administered QT interval-prolonging drugs during hospitalization; (iii) the proportion of these higher-risk patients in whom TdP risk factor monitoring was performed; (iv) proportion of patients with QT(c) interval prolongation who subsequently received QT-prolonging drugs and who experienced further QT(c) interval prolongation.Results: Of 1159 patients enrolled, 259 patients met exclusion criteria, resulting in a final sample size of 900 patients.Patient Characteristics: mean (± SD) age, 65 ± 15 years; female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QT(c) interval prolongation was present in 27.9% of patients on admission; 18.2% had QT(c) interval >500 ms. Of 251 patients admitted with QT(c) interval prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging drugs. Of 166 patients admitted with QT(c) interval >500 ms, 70 (42.2%) were subsequently administered QT interval-prolonging drugs; additional QT(c) interval prolongation ≥60 ms occurred in 57.1% of these patients.Conclusions: QT(c) interval prolongation is common among patients admitted to cardiac units. QT interval-prolonging drugs are commonly prescribed to patients presenting with QT(c) interval prolongation. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
4. APhA2009 House of Delegates: serving the association and the profession.
- Author
-
Weitzel KW, Tisdale JE, and Mattingly J
- Published
- 2009
- Full Text
- View/download PDF
5. Bleeding associated with eptifibatide targeting higher risk patients with acute coronary syndromes: incidence and multivariate risk factors.
- Author
-
Rasty S, Borzak S, and Tisdale JE
- Abstract
The objective of this study was to determine the safety of the glycoprotein IIb/IIIa receptor inhibitor eptifibatide in patients at high risk for adverse clinical outcomes and to determine risk factors for eptifibatide-associated bleeding. Consecutive patients (n = 175) who presented with an acute coronary syndrome and who were at high risk for adverse clinical outcomes were prospectively observed for eptifibatide-associated bleeding, which was classified according to Thrombolysis in Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded arteries (GUSTO) criteria. High risk was defined as unstable angina or non-Q-wave myocardial infarction with at least one of the following: left ventricular ejection fraction < 40%, diabetes mellitus, ST segment depression or transient ST segment elevation, serum [troponin I] > 2.5 ng/mL, and recurrent angina symptoms after initiation of conventional antianginal therapy. Bleeding incidences in the patients in this study were compared with those in the 4722 eptifibatide-treated patients in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial. Compared to PURSUIT patients, the population in this study was similar in age but had a higher proportion of females, African Americans, hypertension, diabetes, prior myocardial infarction, heart failure, and revascularization. Bleeding incidences in this study's patients were similar to or lower than those in the PURSUIT population: TIMI major 1.1% versus 10.8%, TAMI minor 12.6% versus 13.1%, GUSTO severe 1.7% versus 1.5%, GUSTO moderate 3.9% versus 11.3%, and GUSTO mild 19.7% versus 26.1%. Renal dysfunction was an independent risk factor for TIMI (odds ratio = 9.1 ([95% CI= 1.6-52.5]) and GUSTO (odds ratio = 6.1 [95% CI = 1.2-30.0]) bleeding. In conclusion, despite being at higher risk for adverse outcomes, patients administered eptifibatide according to this study's institutional guidelines had comparable or lower bleeding rates than in the PURSUIT trial. Renal dysfunction is an independent risk factor for eptifibatide-induced bleeding. [ABSTRACT FROM AUTHOR]
- Published
- 2002
6. The effect of intravenous haloperidol on QT interval dispersion in critically ill patients: comparison with QT interval prolongation for assessment of risk of Torsades de Pointes.
- Author
-
Tisdale JE, Rasty S, Padhi ID, Sharma ND, and Rosman H
- Abstract
The objective of this study was to determine the effect of intravenous haloperidol on QT interval dispersion in critically ill patients and to compare increases in QT interval dispersion and QTc intervals in patients who developed haloperidol-induced Torsades de Pointes versus those in patients who did not. This was a case-controlled study of 30 critically ill patients who received intravenous haloperidol for delusional agitation. Cases were patients (n = 6) who developed Torsades de Pointes during haloperidol therapy. Controls were patients (n = 24) who did not experience haloperidol-induced Torsades dePointes. QTc intervals were measured and QT interval dispersion was calculated. Haloperidol prolonged QTc interval compared to pretreatment values in Torsades de Pointes patients (606 +/- 61 ms vs. 501 +/- 44 ms, p = 0.007) by a greater magnitude than in patients who did not experience Torsades de Pointes (507 +/- 60 ms vs. 466 +/- 44, p = 0.01). Twelve-lead analysis revealed that QT interval dispersion increased in patients who experienced Torsades de Pointes (from 63 +/- 11 to 95 +/- 22 ms, p = 0.03) but not in those who did not (62 +/- 18 vs. 60 +/- 26 ms, p = 0.66). Analysis of precordial leads only showed no significant haloperidol-associated increases in QTinterval dispersion in eithergroup. The odds of developing haloperidol-induced Torsades de Pointes were highest in patients with QTc interval > 521 ms during haloperidol therapy(odds ratio = 12.1). It was concluded that intravenous haloperidol prolongs QTc intervals in critically ill patients. The degree of prolongation is greater in patients who experience Torsades de Pointes. QT interval dispersion may be increased in patients who develop haloperidol-induced Torsades de Pointes compared with those who do not. However, these effects are dependent on the method of measurement (12 leads vs. precordial leads). In addition, the odds of haloperidol-induced Torsades de Pointes are higherin patients with QTc intervalprolongation compared with increased QT interval dispersion. Therefore, QTc interval determination remains preferable to QT interval dispersion as a means assessment of risk for haloperidol-induced Torsades de Pointes. [ABSTRACT FROM AUTHOR]
- Published
- 2001
7. Drug-induced QT interval prolongation in patients with heart failure with preserved ejection fraction.
- Author
-
Huang CY, Overholser BR, Sowinski KM, Jaynes HA, Kovacs RJ, and Tisdale JE
- Subjects
- Humans, Female, Male, Aged, Retrospective Studies, Middle Aged, Aged, 80 and over, Electrocardiography, Anti-Arrhythmia Agents adverse effects, Risk Factors, Heart Failure physiopathology, Heart Failure drug therapy, Phenethylamines adverse effects, Sotalol adverse effects, Stroke Volume drug effects, Sulfonamides adverse effects, Long QT Syndrome chemically induced, Long QT Syndrome physiopathology, Long QT Syndrome epidemiology
- Abstract
Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) is also associated with an increased risk. Dofetilide and sotalol are potent QT interval-prolonging agents that are frequently used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. We tested the hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol is increased in patients with HFpEF. We conducted a retrospective cohort study conducted using electronic health records from the Indiana Network for Patient Care (January 31, 2010 -May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, we identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no HF (n = 729). QT prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) for QT prolongation were determined by univariate analysis. Adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates. QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7% and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF [OR = 1.98 (95% CI 1.17-3.33)], and in those with HFrEF [OR = 5.23, (3.15-8.67)], compared to those with no evidence of HF. The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
- Full Text
- View/download PDF
8. Pharmacological Management of Cardiac Arrhythmias in the Fetal and Neonatal Periods: A Scientific Statement From the American Heart Association: Endorsed by the Pediatric & Congenital Electrophysiology Society (PACES).
- Author
-
Batra AS, Silka MJ, Borquez A, Cuneo B, Dechert B, Jaeggi E, Kannankeril PJ, Tabulov C, Tisdale JE, and Wolfe D
- Subjects
- Infant, Newborn, United States, Child, Humans, Tachycardia, Fetus, Electrophysiology, American Heart Association, Arrhythmias, Cardiac diagnosis, Arrhythmias, Cardiac drug therapy
- Abstract
Disorders of the cardiac rhythm may occur in both the fetus and neonate. Because of the immature myocardium, the hemodynamic consequences of either bradyarrhythmias or tachyarrhythmias may be far more significant than in mature physiological states. Treatment options are limited in the fetus and neonate because of limited vascular access, patient size, and the significant risk/benefit ratio of any intervention. In addition, exposure of the fetus or neonate to either persistent arrhythmias or antiarrhythmic medications may have yet-to-be-determined long-term developmental consequences. This scientific statement discusses the mechanism of arrhythmias, pharmacological treatment options, and distinct aspects of pharmacokinetics for the fetus and neonate. From the available current data, subjects of apparent consistency/consensus are presented, as well as future directions for research in terms of aspects of care for which evidence has not been established.
- Published
- 2024
- Full Text
- View/download PDF
9. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
- Author
-
Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, Cronin EM, Deswal A, Eckhardt LL, Goldberger ZD, Gopinathannair R, Gorenek B, Hess PL, Hlatky M, Hogan G, Ibeh C, Indik JH, Kido K, Kusumoto F, Link MS, Linta KT, Marcus GM, McCarthy PM, Patel N, Patton KK, Perez MV, Piccini JP, Russo AM, Sanders P, Streur MM, Thomas KL, Times S, Tisdale JE, Valente AM, and Van Wagoner DR
- Subjects
- Humans, United States epidemiology, American Heart Association, Risk Factors, Atrial Fibrillation diagnosis, Atrial Fibrillation therapy, Atrial Fibrillation epidemiology, Cardiology, Thromboembolism
- Abstract
Aim: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation., Methods: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate., Structure: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
10. "Quick flutter skip": midlife women's descriptions of palpitations.
- Author
-
Carpenter JS, Fagan R, Alzahrani MA, Jaynes HA, Tisdale JE, Kovacs RJ, Chen CX, and Draucker CB
- Subjects
- Humans, Female, Middle Aged, Pilot Projects, Case-Control Studies, Communication, Awareness, Behavior Therapy
- Abstract
Objective: The objective of this study is to describe peri- and postmenopausal women's experiences of palpitations (quality, frequency, severity, distress, duration and temporal pattern, aura, associated symptoms, and aggravating/alleviating factors) and related healthcare experiences., Methods: Qualitative descriptive methods were used. Semistructured interviews were conducted with women who reported palpitations and were enrolled in a larger case-control pilot study comparing electrocardiographic results between women with and without palpitations. Authors analyzed women's narratives using standard content analytic procedures., Results: Fourteen participants (mean age, 54.5 y [SD = 4.8 y]; range, 46-62 y; 79% postmenopausal) completed interviews. The interviews revealed that women (a) often had difficulty describing their palpitations until prompted by the interviewer; (b) experienced noteworthy variations in the quality and other dimensions of their palpitations; (c) had a wide variety of healthcare experiences related to their palpitations, including not reporting their symptoms to providers, having providers dismiss their symptoms, and having providers be aware of their symptoms and provide diagnostic tests; and (d) at times, created worst case scenarios (downward shifts) under which they would seek treatment for their palpitations, thus enabling them to minimize their symptoms and avoid healthcare., Conclusion: This study advances understanding of how women describe their palpitations and related healthcare experiences. Findings could have implications for building research and clinical tools to guide assessment, communication, and/or education for patients and/or providers about palpitations and for developing and testing behavioral interventions to address this poorly understood symptom in peri- and postmenopausal women., Competing Interests: Financial disclosures/conflicts of interest: Janet Carpenter received past funding from the University of Wisconsin and Simumetrix. Mofareh Alzahrani was supported by SACM as a graduate student (unrelated to this work). James E. Tisdale receives ongoing funding from National Heart Lung and Blood Institute, American Heart Association, Pharmacotherapy Publications, Inc, and ongoing book royalties from Elsevier and American Society of Health-System Pharmacists. The other authors have nothing to disclose., (Copyright © 2023 by The Menopause Society.)
- Published
- 2023
- Full Text
- View/download PDF
11. Prolonged Exposure to Remdesivir Inhibits the Human Ether-A-Go-Go-Related Gene Potassium Current.
- Author
-
Amarh E, Tisdale JE, and Overholser BR
- Subjects
- Humans, Ether-A-Go-Go Potassium Channels genetics, Potassium, COVID-19 Drug Treatment, Ethers, Potassium Channel Blockers pharmacology, Torsades de Pointes, COVID-19
- Abstract
Abstract: Remdesivir, approved for the treatment of COVID-19, has been associated with heart-rate corrected QT interval (QTc) prolongation and torsade de pointes in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related gene (hERG) -related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney 293 cells stably expressing hERG were treated with various concentrations of remdesivir and GS-441524. The effects of acute and prolonged exposure on hERG-related current were assessed using whole-cell configuration of voltage-clamp protocols. Acute exposure to remdesivir and GS-441524 had no effect on hERG currents and the half-activation voltage (V 1/2 ). Prolonged treatment with 100 nM and 1 µM remdesivir significantly reduced peak tail currents and hERG current density. The propensity for remdesivir to prolong QTc intervals and induce torsade de pointes in predisposed patients warrants further investigation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
12. Multidisciplinary Critical Care Management of Electrical Storm: JACC State-of-the-Art Review.
- Author
-
Jentzer JC, Noseworthy PA, Kashou AH, May AM, Chrispin J, Kabra R, Arps K, Blumer V, Tisdale JE, and Solomon MA
- Subjects
- Humans, Arrhythmias, Cardiac, Anti-Arrhythmia Agents therapeutic use, Defibrillators, Implantable, Heart Transplantation, Catheter Ablation, Tachycardia, Ventricular therapy
- Abstract
Electrical storm (ES) reflects life-threatening cardiac electrical instability with 3 or more ventricular arrhythmia episodes within 24 hours. Identification of underlying arrhythmogenic cardiac substrate and reversible triggers is essential, as is interrogation and programming of an implantable cardioverter-defibrillator, if present. Medical management includes antiarrhythmic drugs, beta-adrenergic blockade, sedation, and hemodynamic support. The initial intensity of these interventions should be matched to the severity of ES using a stepped-care algorithm involving escalating treatments for higher-risk presentations or recurrent ventricular arrhythmias. Many patients with ES are considered for catheter ablation, which may require the use of temporary mechanical circulatory support. Outcomes after ES are poor, including frequent ES recurrences and deaths caused by progressive heart failure and other cardiac causes. A multidisciplinary collaborative approach to the management of ES is crucial, and evaluation for heart transplantation or palliative care is often appropriate, even for patients who survive the initial episode., Competing Interests: Funding Support and Author Disclosures No extramural funding was directly involved in the conduct of this research. Dr Noseworthy has received research funding from National Institutes of Health (including the National Heart, Lung, and Blood Institute [R21AG 62580-1, R01HL 131535-4, R01HL 143070-2] and the National Institute on Aging [R01AG 062436-1]), Agency for Healthcare Research and Quality (R01HS 25402-3), U.S. Food and Drug Administration (FD 06292), and the American Heart Association (18SFRN34230146); he and Mayo Clinic have filed patents related to the application of artificial intelligence to electrocardiography for diagnosis and risk stratification and have licensed several artificial intelligence–electrocardiography algorithms to Anumana; he and Mayo Clinic are involved in potential equity/royalty relationship with AliveCor; he has served as a study investigator in an ablation trial sponsored by Medtronic; and has served on an expert advisory panel for OptumLabs. Dr Kashou is supported by the National Institutes of Health (T32 HL007111) and the Department of Cardiovascular Medicine at Mayo Clinic. Dr May has equity rights and possibly royalties received by the Mayo Clinic from Anumana Inc. Dr Chrispin has served on the Advisory Board for Biosense Webster; and has received honorarium from Abbott for educational activities. Dr Tisdale is supported by the National Heart, Lung, and Blood Institute, the American Heart Association, and the Indiana Clinical and Translational Sciences Institute. Dr Solomon is employed by the National Institutes of Health; and has received research support from the National Institutes of Health Clinical Center intramural research funds; this written work does not represent the official opinion of the U.S. government. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
13. Relationship between a risk score for QT interval prolongation and mortality across rural and urban inpatient facilities.
- Author
-
Tan MS, Heise CW, Gallo T, Tisdale JE, Woosley RL, Antonescu CC, Gephart SM, and Malone DC
- Subjects
- Humans, Female, Aged, Male, Inpatients, Electrocardiography, Risk Factors, DNA-Binding Proteins, Long QT Syndrome etiology, Torsades de Pointes etiology
- Abstract
Objectives: To evaluate the relationship between a modified Tisdale QTc-risk score (QTc-RS) and inpatient mortality and length of stay in a broad inpatient population with an order for a medication with a known risk of torsades de pointes (TdP)., Background: Managing the risk of TdP is challenging due to the number of medications with known risk of TdP and the complexity of precipitating factors. A model to predict risk of mortality may be useful to guide treatment decisions., Methods: This was a retrospective observational study using inpatient data from 28 healthcare facilities in the western United States. This risk score ranges from zero to 23 with weights applied to each risk factor based on a previous validation study. Logistic regression and a generalized linear model were performed to assess the relationship between QTc-RS and mortality and length of stay., Results: Between April and December 2020, a QTc-RS was calculated for 92,383 hospitalized patients. Common risk factors were female (55.0%); age > 67 years (32.1%); and receiving a medication with known risk of TdP (24.5%). A total of 2770 (3%) patients died during their hospitalization. Relative to patients with QTc-RS < 7, the odds ratio for mortality was 4.80 (95%CI:4.42-5.21) for patients with QTc-RS = 7-10 and 11.51 (95%CI:10.23-12.94) for those with QTc-RS ≥ 11. Length of hospital stay increased by 0.7 day for every unit increase in the risk score (p < 0.0001)., Conclusion: There is a strong relationship between increased mortality as well as longer duration of hospitalization with an increasing QTc-RS., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
14. Palpitations across the menopause transition in SWAN: trajectories, characteristics, and associations with subclinical cardiovascular disease.
- Author
-
Carpenter JS, Cortés YI, Tisdale JE, Sheng Y, Jackson EA, Barinas-Mitchell E, and Thurston RC
- Subjects
- Female, Humans, Carotid Intima-Media Thickness, Menopause physiology, Postmenopause physiology, Perimenopause physiology, Risk Factors, Cardiovascular Diseases epidemiology
- Abstract
Objective: Our objectives were to identify trajectories of palpitations over the menopause transition, characterize them, and examine associations with subclinical cardiovascular disease (CVD)., Methods: We analyzed the following data from the multisite, multiethnic SWAN (Study of Women Across the Nation): reported palpitations occurrence over time; baseline sociodemographic, reproductive, medication, and health-related factors; and follow-up visit subclinical CVD (carotid atherosclerosis, vascular stiffness). Trajectories of palpitations (n = 3,276), their characteristics, and their associations with subclinical CVD (n = 1,559) were identified using group-based trajectory modeling and linear and logistic regression models., Results: Three trajectories emerged: high probability of palpitations in perimenopause to early postmenopause diminishing in late postmenopause (15.9% of women), moderate probability of palpitations in perimenopause to early postmenopause diminishing in late postmenopause (34.3%), and sustained low probability of palpitations (49.8%). In the fully adjusted multivariable model, the high probability group had a more adverse reproductive and health-related profile at baseline (higher gravidity, early perimenopause, vasomotor symptoms, poorer overall health, higher depressive symptoms, higher perceived stress, greater sleep problems, higher blood pressure). In fully adjusted multivariable models, palpitation trajectories were not related to atherosclerosis or arterial stiffness., Conclusions: Distinct patterns of palpitations emerged, with a substantial portion of women having palpitations during the perimenopause and early postmenopause. Palpitations were not associated with subclinical CVD. Findings can help identify women at risk of palpitations during the menopause transition who may need symptom relief., Competing Interests: Financial disclosure/conflicts of interest: J.S.C. reports personal fees from Mapi/ICON and the University of Wisconsin Milwaukee. J.E.T. reports institutional fees from the NIH, the American Heart Association, and Agency for Healthcare Quality and Research; funding from Pharmacotherapy Publications Inc; an annual stipend for serving as Scientific Editor Nova Southeastern University; honorarium for giving a presentation at a symposium American Society of Health; book royalties from Systems Pharmacists. E.A.J. has research support from NIH and Amgen, is a consultant for UpToDate and McKesson, serves on the Editorial Board for American Heart Association, is a consultant to American College of Cardiology, and is an expert witness for DeBlase Brown Everly LLP. R.C.T. is a consultant/advisory board member for Astellas, Bayer, Vira Health, and Happify Health and was a past consultant for Pfizer and Virtue Health. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)
- Published
- 2023
- Full Text
- View/download PDF
15. Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer.
- Author
-
Rowe EJ, Shugg T, Ly RC, Philips S, Rosenman MB, Callaghan JT, Radovich M, Overholser BR, Schneider BP, Tisdale JE, and Skaar TC
- Abstract
Introduction: Drug-induced prolongation of the heart rate-corrected QT interval (QTc) is associated with increased risk for the potentially fatal arrhythmia torsades de pointes. Due to arrhythmia risk, clinical trials with cancer therapeutics often exclude patients based on thresholds for QTc prolongation. Our objective was to assess associations between prescriptions for QT-prolonging drugs and the odds of meeting cancer trial exclusionary QTc thresholds in a cohort of adults with advanced cancer., Methods: Electronic health records were retrospectively reviewed for 271 patients seen at our institutional molecular solid tumor clinic. Collected data included demographics, QTc measurements, ventricular arrhythmia-related diagnoses, and all inpatient and outpatient prescriptions. Potential associations were assessed between demographic and clinical variables, including prescriptions for QT-prolonging drugs, and QTc measurements., Results: Women had longer median QTc measurements than men ( p = 0.030) and were prescribed more QT-prolonging drugs during the study ( p = 0.010). In all patients, prescriptions for QT-prolonging drugs were associated with longer median and maximum QTc measurements at multiple assessed time points (i.e., for QT-prolonging drugs prescribed within 10, 30, 60, and 90 days of QTc measurements). Similarly, the number of QT-prolonging drugs prescribed was correlated with longer median and maximum QTc measurements at multiple time points. Common QTc-related exclusionary criteria were collected from a review of ClinicalTrials.gov for recent cancer clinical trials. Based on common exclusion criteria, prescriptions for QT-prolonging drugs increased the odds of trial exclusion., Conclusion: This study demonstrates that prescriptions for QT-prolonging drugs were associated with longer QTc measurements and increased odds of being excluded from cancer clinical trials., Competing Interests: MRa reports financial connections to ArQule, Inc., Boston Biomedical, Inc., Eli Lilly and Company, Immunomedics, Inc., LifeOmic, Inc., Macrogenics, Inc., and Tyme Technologies, Inc., and is currently an employee of Caris Life Sciences, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rowe, Shugg, Ly, Philips, Rosenman, Callaghan, Radovich, Overholser, Schneider, Tisdale and Skaar.)
- Published
- 2022
- Full Text
- View/download PDF
16. Testosterone does not shorten action potential duration in Langendorff-perfused rabbit ventricles.
- Author
-
Ueoka A, Sung YL, Liu X, Rosenberg C, Chen Z, Everett TH 4th, Rubart M, Tisdale JE, and Chen PS
- Subjects
- Animals, Female, Rabbits, Humans, Male, Testosterone pharmacology, Action Potentials, Heart, Heart Ventricles, Long QT Syndrome, Atrioventricular Block
- Abstract
Background: Women have longer baseline QT intervals than men. Because previous studies showed that testosterone and 5α-dihydrotestosterone shorten the ventricular action potential duration (APD) in animal models, differential testosterone concentrations may account for the sex differences in QT interval., Objective: The purpose of this study was to test the hypothesis that testosterone shortens the APD in Langendorff-perfused rabbit ventricles., Methods: We performed optical mapping studies in hearts with or without testosterone administration. Acute studies included 26 hearts using 2 different protocols, including 17 without and 9 with atrioventricular (AV) block. For chronic studies, we implanted testosterone pellets subcutaneously in 7 female rabbits for 2-3 weeks before optical mapping studies during complete AV block. Six rabbits without pellet implantation served as controls., Results: The hearts in the acute studies were paced with a pacing cycle length (PCL) of 200-300 ms and mapped at baseline and after administration of 1 nM, 10 nM, 100 nM, and 3 μM of testosterone. There was no shortening of APD
80 at any PCL. Instead, a lengthening of APD80 was noted at higher concentrations. There were no sex differences in testosterone responses. In chronic studies, heart rates were 136 ± 5 bpm before and 148 ± 9 bpm after (P = .10) while QTc intervals were 314 ± 9 ms before and 317 ± 99 ms after (P = .69) testosterone pellet implantation, respectively. Overall, ventricular APD80 in the pellet group was longer than in the control group at 300- to 700-ms PCL., Conclusion: Testosterone does not shorten ventricular repolarization in rabbit hearts., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
17. Clinician Satisfaction With Advanced Clinical Decision Support to Reduce the Risk of Torsades de Pointes.
- Author
-
Gallo T, Heise CW, Woosley RL, Tisdale JE, Antonescu CC, Gephart SM, and Malone DC
- Subjects
- Humans, Personal Satisfaction, Risk Factors, Decision Support Systems, Clinical, Torsades de Pointes prevention & control
- Abstract
Objectives: Clinical decision support (CDS) can potentially help clinicians identify and manage patients who are at risk for torsades de pointes (TdP). However, computer alerts are often ignored and might contribute to alert fatigue. The goals of this project were to create an advanced TdP CDS advisory that presents patient-specific, relevant information, including 1-click management options, and to determine clinician satisfaction with the CDS., Methods: The advanced TdP CDS was developed and implemented across a health system comprising 29 hospitals. The advisory presents patient-specific information including relevant risk factors, laboratory values, and 1-click options to help manage the condition in high-risk patients. A short electronic survey was created to gather clinician feedback on the advisory., Results: After implementation, an email invitation to complete the anonymous advisory-related survey was sent to 442 clinicians who received the advisory. Among the 38 respondents, feedback was generally positive, with 79% of respondents reporting that the advisory helps them care for their patients and 87% responding that alternative actions for them to consider were clearly specified. However, 46% of respondents indicated the alert appeared too frequently., Conclusions: Advanced TdP risk CDS that provides relevant, patient-specific information and 1-click management options can be generally viewed favorably by clinicians who receive the advisory., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
18. Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes.
- Author
-
Gallo T, Heise CW, Woosley RL, Tisdale JE, Tan MS, Gephart SM, Antonescu CC, and Malone DC
- Subjects
- DNA-Binding Proteins, Electrocardiography, Humans, Retrospective Studies, Decision Support Systems, Clinical, Long QT Syndrome chemically induced, Torsades de Pointes chemically induced, Torsades de Pointes diagnosis
- Abstract
Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high-risk medications in patients at risk of TdP, but alerts are often ignored. Other risk-management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient-specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8-month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class ( P <0.05 for all actions). Conclusions A modified Tisdale QT risk score-based CDS that offered relevant single-click management options yielded a high action/response rate. Actions taken by clinicians varied depending on the class of the medication that evoked the TdP risk advisory, but the most frequent was ordering an ECG.
- Published
- 2022
- Full Text
- View/download PDF
19. Drug Interactions Affecting Oral Anticoagulant Use.
- Author
-
Mar PL, Gopinathannair R, Gengler BE, Chung MK, Perez A, Dukes J, Ezekowitz MD, Lakkireddy D, Lip GYH, Miletello M, Noseworthy PA, Reiffel J, Tisdale JE, and Olshansky B
- Subjects
- Administration, Oral, Cytochrome P-450 CYP3A therapeutic use, Dabigatran, Drug Interactions, Hemorrhage chemically induced, Humans, Pyridones adverse effects, Rivaroxaban therapeutic use, Warfarin adverse effects, Anticoagulants adverse effects, Atrial Fibrillation complications
- Abstract
Oral anticoagulants (OACs) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants are susceptible to drug-drug interactions (DDIs). DDIs are an important cause of adverse drug reactions and exact a large toll on the health care system. DDI for warfarin mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.
- Published
- 2022
- Full Text
- View/download PDF
20. Drug Interactions Affecting Antiarrhythmic Drug Use.
- Author
-
Mar PL, Horbal P, Chung MK, Dukes JW, Ezekowitz M, Lakkireddy D, Lip GYH, Miletello M, Noseworthy PA, Reiffel JA, Tisdale JE, Olshansky B, and Gopinathannair R
- Subjects
- Anti-Arrhythmia Agents adverse effects, Anti-Bacterial Agents therapeutic use, Arrhythmias, Cardiac chemically induced, Arrhythmias, Cardiac drug therapy, Drug Interactions, Humans, Amiodarone therapeutic use, Long QT Syndrome chemically induced, Long QT Syndrome drug therapy
- Abstract
Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.
- Published
- 2022
- Full Text
- View/download PDF
21. Effect of menopausal symptom treatment options on palpitations: a systematic review.
- Author
-
Sheng Y, Carpenter JS, Elomba CD, Alwine JS, Yue M, Chen CX, and Tisdale JE
- Subjects
- Female, Humans, Menopause, Cognitive Behavioral Therapy, Isoflavones
- Abstract
This systematic review provides an overview of the effects of menopausal symptom treatment options on palpitations, defined as feelings of missed or exaggerated heart beats, reported by perimenopausal and postmenopausal women. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searches were conducted in PubMed, CINAHL and PsycINFO to identify articles meeting pre-specified inclusion criteria. Of 670 unique articles identified, 37 were included in the review. Treatments included drug therapies and non-drug therapies. Palpitations were studied as an outcome in 89% of articles and as an adverse effect in 11%. Articles provided mostly level II/III evidence due to their design and/or small sample sizes. Based on available evidence, no therapies can be fully recommended for clinical practice. Only some hormonal agents (e.g. estradiol) can be recommended with caution based on some positive evidence for reducing palpitation prevalence or severity. However, other drug therapies (e.g. moxonidine, atenolol), dietary supplementary treatments (e.g. isoflavones, Rheum rhaponticum , sage), cognitive-behavioral intervention and auricular acupressure cannot be recommended given the existing evidence. Additional well-designed randomized controlled treatment trials focusing on palpitations during the menopause transition as an inclusion criteria and outcome are needed to advance the field.
- Published
- 2022
- Full Text
- View/download PDF
22. Correlates of palpitations during menopause: A scoping review.
- Author
-
Carpenter JS, Sheng Y, Pike C, Elomba CD, Alwine JS, Chen CX, and Tisdale JE
- Subjects
- Cross-Sectional Studies, Exercise, Female, Humans, Postmenopause, Menopause, Quality of Life
- Abstract
Objective: Palpitations during peri- and post-menopause are common. It is unclear what variables are related to palpitations in peri- and post-menopausal women. The purpose of this scoping review was to summarize potential correlates of palpitations in women transitioning through menopause., Methods: The review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Authors included English-language, full-length, peer-reviewed, cross-sectional research articles on palpitations in menopausal women published through December 18, 2021, from PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO searches. Following de-duplication, screening of titles and abstracts, and review of full-texts, independent reviewers extracted data on variables studied in relationship to palpitations from 84 articles and resolved discrepancies. Authors extracted data on (1) demographic, clinical, biomarker, and symptom/quality of life variables and (2) data analysis method (bivariate, multivariate). Authors classified each variable as a likely, unlikely, or unclear correlate of palpitations., Results: Articles were diverse in region of origin, sample sizes, and variables assessed in relationship to palpitations. Evidence for any one variable was sparse. Likely correlates of palpitations included race/ethnicity, lower physical activity, worse vasomotor symptoms (VMSs), worse sleep, and worse quality of life. Unlikely correlates included age, employment, education, marital status, socioeconomic status, comorbidities, body mass index, and sexual difficulties. Unclear correlates due to equivocal evidence were menopausal status, smoking, and depression. Unclear correlates due to insufficient evidence (less than three articles) included all of the assessed biomarkers, anxiety, and stress., Conclusion: Likely correlates were identified including race/ethnicity, physical activity, VMS, sleep, and quality of life. However, additional research is needed to better understand potential correlates of palpitations.
- Published
- 2022
- Full Text
- View/download PDF
23. MsFLASH analysis of diurnal salivary cortisol and palpitations in peri- and postmenopausal women.
- Author
-
Carpenter JS, Tisdale JE, Larson JC, Sheng Y, Chen CX, Von Ah D, Kovacs R, Reed SD, Thurston RC, and Guthrie KA
- Subjects
- Arrhythmias, Cardiac, Child, Preschool, Circadian Rhythm, Female, Humans, Hydrocortisone, Postmenopause, Saliva, Stress, Psychological, Sleep Initiation and Maintenance Disorders, Yoga
- Abstract
Objective: To evaluate the relationship between diurnal salivary cortisol patterns and distress from heart palpitations in midlife women., Methods: We analyzed baseline data from 293 women who were eligible for a 3 × 2 factorial trial of exercise or yoga versus routine activity, and omega-3 fish oil versus placebo for vasomotor symptoms. Women self-collected salivary cortisol using swabs at four time points over 2 consecutive days and reported distress from heart racing or pounding during the past 2 weeks using a single item. Sample description and covariate data included demographics, clinical data, vasomotor symptom frequency from daily diaries, medication use, and validated questionnaires on depression, stress, and insomnia (Patient Health Questionnaire-8, Perceived Stress Scale, and Insomnia Severity index). Data were analyzed using descriptive statistics, chi-square and t tests, and repeated measure linear regression models., Results: Participants were on average 54.6 (SD = 3.6) years old, most were White (67%) postmenopausal (84%), and 26% reported distress related to palpitations. In adjusted models, the morning (wake plus 30-min) geometric mean daily salivary cortisol concentrations were significantly more blunted in those with distress from palpitations compared with those without distress (P ≤ 0.03). When all covariates were controlled, distress from palpitations was the sole significant predictor of wake plus 30-minute cortisol (-0.25 [-0.45 to -0.04], P = 0.02)., Conclusions: Palpitations among midlife women may be associated with blunted morning cortisol, and this relationship is not explained by demographics, clinical variables, vasomotor symptoms, medications, depression, stress, or insomnia., Competing Interests: Financial disclosures/conflicts of interest: J.S.C. reports personal fees from Kappa Santé and the University of Wisconsin Milwaukee. R.C.T. reports consulting fees from Astellas Pharma Inc, Pfizer, Proctor & Gamble, and Virtue Health. S.D.R. receives grant support from Bayer, AG, and receives royalties from UpToDate. J.E.T.'s institution receives funding from Indiana Clinical & Translational Sciences Institute, National Heart, Lung, and Blood Institute, Agency for Healthcare Research & Quality, and American Heart Association. J.E.T. receives a stipend for services as Scientific Editor of Pharmacotherapy (journal). D.V.A. receives honorarium for work for NIH/NCI for advisory board membership Palliative and Supportive Care PDQ. J.C.L., Y.S., C.X.C., R.K., and K.A.G. have nothing to disclose., (Copyright © 2021 by The North American Menopause Society.)
- Published
- 2021
- Full Text
- View/download PDF
24. Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men.
- Author
-
Tomaselli Muensterman E, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, and Tisdale JE
- Subjects
- Administration, Cutaneous, Administration, Oral, Aged, Aged, 80 and over, Anti-Arrhythmia Agents administration & dosage, Anti-Arrhythmia Agents pharmacology, Cross-Over Studies, Double-Blind Method, Electrocardiography drug effects, Humans, Male, Progesterone administration & dosage, Progesterone therapeutic use, Prospective Studies, Sulfonamides administration & dosage, Sulfonamides pharmacology, Long QT Syndrome chemically induced, Long QT Syndrome drug therapy, Testosterone administration & dosage, Testosterone therapeutic use
- Abstract
We have previously reported that transdermal testosterone attenuates drug-induced QT interval lengthening in older men. However, it is unknown whether this is due to modulation of early ventricular repolarization, late repolarization, or both. In a secondary analysis of a prospective, randomized, double-blind, placebo-controlled three-way crossover study, we determined if transdermal testosterone and oral progesterone attenuate drug-induced lengthening of early and late ventricular repolarization, represented by the electrocardiographic measurements J-T
peak c and Tpeak -Tend , respectively, as well as Tpeak -Tend /QT, a measure of transmural dispersion of repolarization. Male volunteers ≥ 65 years of age (n = 14) were randomized to receive transdermal testosterone 100 mg, oral progesterone 400 mg, or matching transdermal/oral placebo daily for 7 days. On the morning following the seventh day, subjects received intravenous ibutilide 0.003 mg/kg, after which electrocardiograms were performed serially. One subject was excluded due to difficulty in T-wave interpretation. Pre-ibutilide J-Tpeak c was lower during the testosterone phase than during progesterone and placebo (216 ± 23 vs. 227 ± 28 vs. 227 ± 21 ms, P = 0.002). Maximum post-ibutilide J-Tpeak c was also lower during the testosterone phase (233 ± 22 vs. 246 ± 29 vs. 248 ± 23 ms, P < 0.0001). Pre-ibutilide Tpeak -Tend was not significantly different during the three phases, but maximum post-ibutilide Tpeak -Tend was lower during the testosterone phase (80 ± 12 vs. 89 ± 18 vs. 86 ± 15 ms, P = 0.002). Maximum Tpeak -Tend /QT was also lower during the testosterone phase (0.199 ± 0.023 vs. 0.216 ± 0.035 vs. 0.209 ± 0.031, P = 0.005). Progesterone exerted minimal effect on drug-induced lengthening of J-Tpeak c, and no effect on Tpeak -Tend or Tpeak -Tend /QT. Transdermal testosterone attenuates drug-induced lengthening of both early and late ventricular repolarization in older men., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2021
- Full Text
- View/download PDF
25. Accuracy of a single-lead mobile smartphone electrocardiogram for QT interval measurement in patients undergoing maintenance methadone therapy.
- Author
-
Titus-Lay EN, Jaynes HA, Tomaselli Muensterman E, Ott CA, Walroth TA, Williams G, Moe PR, Wilbrandt M, and Tisdale JE
- Subjects
- Adult, Female, Humans, Male, Methadone adverse effects, Middle Aged, Opioid-Related Disorders drug therapy, Prospective Studies, Reproducibility of Results, Young Adult, Electrocardiography methods, Long QT Syndrome chemically induced, Long QT Syndrome diagnosis, Smartphone
- Abstract
Study Objective: Methadone is associated with QT interval prolongation and torsades de pointes. Expert panel recommendations advocate a pre-methadone electrocardiogram (ECG) and another ECG at 30 days of therapy in patients with risk factors. Some guidelines recommend a pre-methadone ECG and routine ECG monitoring in all methadone patients, but this is controversial due to the resources required. Availability of a convenient, less resource-intensive method of ECG monitoring for patients taking methadone is desirable. The objective of this study was to assess the accuracy of a handheld smartphone ECG (iECG) for QT measurement in patients on maintenance methadone therapy in an urban opioid treatment program., Design: Prospective study., Setting: Urban opioid treatment program., Patients: n = 115 patients in normal sinus rhythm who were on steady-state maintenance methadone therapy INTERVENTION: Patients (n = 115) underwent a simultaneous 12-lead ECG and a single-lead iECG., Measurements and Main Results: The first three QT and RR intervals from lead II of the 12-lead ECG and simulated lead I from the iECG were compared using the Bland-Altman analysis of measurement agreement. Mean [± standard deviation) age was 34 ± 11 years; 71% were female, 75% were white. Compared to the 12-lead ECG, the iECG was associated with a QTc bias of - 0.14 ms (SD = 12 ms, 95% CI = -2.4 to 2.1 ms). The absolute mean difference in QTc between the two methods was 9.5 ± 7.1 ms. For identification of patients with methadone-associated QTc prolongation, the iECG performed moderately well [c-statistic 0.97 (95% CI 0.91-0.99); sensitivity and specificity 75% (95% CI 43-95%) and 99% (95% CI 94-99%), respectively]. The positive and negative likelihood ratios of the iECG for identifying patients with methadone-associated QTc prolongation were 77.25 (95% CI 10.69 to 558.18) and 0.25 (95% CI 0.09 to 0.67), respectively, while the positive and negative predictive values were 90% (95% CI 56-99%) and 97% (95% CI 92-99%), respectively. The accuracy of the iECG for identifying patients with QTc prolongation was 97% (95% CI 91-99%)., Conclusion: A handheld smartphone ECG is accurate for QT interval measurement in patients taking maintenance methadone therapy, and its performance is moderately good for identifying patients with methadone-associated QTc prolongation., (© 2021 Pharmacotherapy Publications, Inc.)
- Published
- 2021
- Full Text
- View/download PDF
26. Review of menopausal palpitations measures.
- Author
-
Sheng Y, Carpenter JS, Elomba CD, Alwine JS, Yue M, Pike CA, Chen CX, and Tisdale JE
- Abstract
Palpitations are reported commonly by women around the time of menopause as skipped, missed, irregular, and/or exaggerated heartbeats or heart pounding. However, much less is known about palpitations than other menopausal symptoms such as vasomotor symptoms. The objective of this review was to integrate evidence on menopausal palpitations measures. Keyword searching was done in PubMed, CINAHL, and PsycINFO for English-language, descriptive articles containing data on menopause and palpitations and meeting other pre-specified inclusion criteria. Of 670 articles, 110 met inclusion criteria and were included in the review. Results showed that 11 different measures were used across articles, with variability within and between measures. Inconsistencies in the wording of measurement items, recall periods, and response options were observed even when standardized measures were used. Most measures were limited to assessing symptom presence and severity. Findings suggest that efforts should be undertaken to (1) standardize conceptual and operational definitions of menopausal palpitations and (2) develop a patient-friendly, conceptually clear, psychometrically sound measure of menopausal palpitations.
- Published
- 2021
- Full Text
- View/download PDF
27. A Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) Investigation of Self-Reported Menopausal Palpitation Distress.
- Author
-
Carpenter JS, Tisdale JE, Chen CX, Kovacs R, Larson JC, Guthrie KA, Ensrud KE, Newton KM, and LaCroix AZ
- Subjects
- Female, Hot Flashes epidemiology, Humans, Menopause, Self Report, Quality of Life, Sleep Initiation and Maintenance Disorders
- Abstract
Background: Study to describe the degree of menopausal palpitation distress and its demographic, clinical, symptom, and quality-of-life (QOL) correlates. Analysis of existing, baseline, data from peri- and postmenopausal women, 42 to 62 years of age, who participated in the Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) clinical trials testing interventions for vasomotor symptoms ( n = 759). Up to 46.8% of menopausal women report having palpitations, yet the symptom is relatively understudied. Little is known about palpitation distress or its correlates. Materials and Methods: Degree of distress from "heart racing or pounding" was self-reported over the past two weeks as "not at all," "a little bit," "moderately," "quite a bit," or "extremely." Other measures included self-report forms, clinic-verified body mass index (BMI), vasomotor symptom diaries, and validated symptom and QOL tools. Results: The percentage who reported palpitation distress was 19.6%, 25.2%, and 33.5% in the three trials or 25.0% overall. In multivariate analysis, the odds of reporting palpitation distress was lower in past smokers (odds ratio [OR] = 0.59 [95% confidence interval (CI) 0.38-0.90]) and current smokers (OR = 0.48 [0.27-0.87]) relative to never-smokers and lower with every 5 kg/m
2 higher BMI (OR = 0.82 [0.69-0.98]).The odds of reporting palpitation distress was higher with every five point more severe insomnia (OR = 1.28 [1.05-1.54]), five point worse depressive symptoms (OR = 1.47 [1.11-1.95]), five point worse perceived stress (OR = 1.19 [1.01-1.39]), and one point worse menopausal QOL (OR = 1.29 [1.06-1.57]). Conclusions: Menopausal palpitation distress is common and associated with demographic, clinical, symptom, and QOL factors. Findings can be used for screening in clinical practice and to justify additional research on this understudied symptom.- Published
- 2021
- Full Text
- View/download PDF
28. Methadone-associated QT interval prolongation in patients undergoing maintenance therapy in an urban opioid treatment program.
- Author
-
Titus-Lay EN, Jaynes HA, Tomaselli Muensterman E, Walroth TA, Ott CA, Desta Z, Williams G, Moe PR, Wilbrandt M, and Tisdale JE
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Prospective Studies, Substance Abuse Treatment Centers, Urban Health Services, Young Adult, Long QT Syndrome chemically induced, Methadone adverse effects, Opioid-Related Disorders drug therapy
- Abstract
Study Objective: Methadone is associated with QT interval prolongation and torsades de pointes. The objective of this study was to (a) determine the incidence of QT interval prolongation among patients on maintenance methadone therapy in an urban opioid treatment program (OTP), (b) compare characteristics of patients who developed methadone-associated QT prolongation with those who did not develop QT prolongation, and (c) investigate the relationship between QT interval prolongation and stereospecific serum methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)] concentrations., Design: Prospective study., Setting: Urban opioid treatment program (OTP)., Patients: n = 93 patients on maintenance methadone therapy in an urban OTP., Intervention: Patients underwent a 12-lead electrocardiogram (ECG) prior to initiating methadone and again during steady-state maintenance methadone therapy. In a subset (n = 43), blood was obtained to determine serum (S)- and (R)-methadone and (S)- and (R)-EDDP concentrations, which were compared in patients who developed Bazett's-corrected QT (QTc) prolongation [≥470 ms (men) or ≥480 ms (women) and/or ≥60 ms lengthening from pretreatment value] with those who did not have QTc prolongation., Measurements and Main Results: Mean [± standard deviation (SD)] age was 36 ± 12 years; 73% were female, and 74% were white. QTc prolongation occurred in 14 (15.1%) patients. Patients who developed QTc prolongation were older (41 ± 13 vs. 35 ± 9 years, p = 0.03) and had a longer pre-methadone QTc compared with those who did not have QTc prolongation (429 ± 11 vs. 420 ± 20 ms, respectively, p = 0.02). Serum (S)-methadone concentrations were higher in patients with QTc prolongation compared to patients without prolongation (199 ± 81 vs. 128 ± 68 ng/ml, respectively, p = 0.01), whereas the difference in serum (R)-methadone concentrations between the groups did not reach significance (189 ± 68 vs. 125 ± 60 ng/ml, respectively, p = 0.08). Serum (R)-methadone concentrations correlated with QTc intervals [R
2 = 0.15 (95% confidence interval (CI) 0.11-0.62, p = 0.0009)]. The correlation between serum (S)-methadone concentrations and QTc did not reach significance [R2 = 0.08 (95% CI -0.01 to 0.54, p = 0.06)]. Serum (S)-and (R)-EDDP concentrations were not significantly different between the groups and did not significantly correlate with QTc intervals., Conclusions: Approximately 15% of patients taking maintenance methadone therapy developed QT interval prolongation. Both serum (S)- and (R)-methadone concentrations, but not (S)- or (R)-EDDP, contribute to methadone-associated QT prolongation., (© 2020 Pharmacotherapy Publications, Inc.)- Published
- 2021
- Full Text
- View/download PDF
29. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association.
- Author
-
Tisdale JE, Chung MK, Campbell KB, Hammadah M, Joglar JA, Leclerc J, and Rajagopalan B
- Subjects
- Risk Factors, United States epidemiology, American Heart Association, Arrhythmias, Cardiac chemically induced, Arrhythmias, Cardiac diagnosis, Arrhythmias, Cardiac epidemiology, Arrhythmias, Cardiac therapy, Electrocardiography
- Abstract
Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient's arrythmia could be drug-induced is important.
- Published
- 2020
- Full Text
- View/download PDF
30. Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.
- Author
-
Tisdale JE, Jaynes HA, Overholser BR, Sowinski KM, Fisch MD, Rodgers JE, Aldemerdash A, Hsu CC, Wang N, Muensterman ET, Rao VU, and Kovacs RJ
- Subjects
- Aged, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Anti-Arrhythmia Agents administration & dosage, Electrocardiography drug effects, Female, Humans, Male, Stroke Volume drug effects, Ventricular Function, Left drug effects, Heart Failure drug therapy, Heart Failure physiopathology, Sulfonamides administration & dosage
- Abstract
Background: Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown., Methods and Results: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration vs time curves, and baseline Fridericia-corrected QT (QT
F ) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTF vs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P= .04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P = .03) indicating greater QTF interval exposure. Maximum QTF (454 ± 15 vs 443 ± 22 ms, P = .18) and maximum percent increase in QTF from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P = .10) in the 2 groups were not significantly different., Conclusions: HFpEF is associated with enhanced response to drug-induced QT interval lengthening., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
31. Chloroquine and Hydroxychloroquine in the Era of SARS - CoV2: Caution on Their Cardiac Toxicity.
- Author
-
Bauman JL and Tisdale JE
- Subjects
- Chloroquine pharmacokinetics, Chloroquine therapeutic use, Humans, Hydroxychloroquine pharmacokinetics, Hydroxychloroquine therapeutic use, Risk Factors, Torsades de Pointes chemically induced, Cardiotoxicity, Chloroquine toxicity, Hydroxychloroquine toxicity, SARS-CoV-2, COVID-19 Drug Treatment
- Published
- 2020
- Full Text
- View/download PDF
32. Progesterone Metabolites Inhibit the Human Ether-a-go-go-Related Gene and Predict QT Interval Length.
- Author
-
Shugg T, Egly C, Stamatkin CW, Patil AS, Tisdale JE, and Overholser BR
- Abstract
A decrease in the human ether-a-go-go-related gene (hERG/KCNH2)-related channel has been linked to intrauterine fetal death. The formation of cytochrome P450 (CYP) 3A-mediated progesterone metabolites, 6-beta-hydroxy-progesterone (6β-OHP) and 16α-hydroxy-progesterone (16α-OHP), is variable among adults and differs from fetal metabolism. The primary objective of this study was to assess the potential for progesterone metabolites to inhibit hERG-related current and predict QTc intervals. Whole-cell voltage-clamp electrophysiology was performed on human embryonic kidney 293 cells stably expressing hERG exposed to progesterone or metabolites. Both 6β-OHP and 16α-OHP positively shifted the voltage dependence of activation relative to vehicle from -4.0 ± 0.8 to -0.3 ± 0.8 mV, P < .01; and 1.0 ± 0.6 mV, P < .01, respectively. In addition, 6β-OHP decreased maximal outward tail currents from 49.4 ± 4.9 to 32.5 ± 4.1 pA/pF, P < 0.01, and reduced the expression of fully glycosylated hERG by 42%. Healthy female subjects were administered progesterone 400 mg orally for 7 days, ibutilide 0.003 mg/kg was infused, and serial electrocardiograms and blood samples collected. Relationships between rate-corrected QT intervals (QTcI) with circulating hormones and metabolites were assessed. The 6β-OHP and 16α-OHP metabolites were independent predictors of QTcI intervals prior to and following ibutilide administration. In conclusion, the progesterone metabolites formed via CYP3A cause inhibitory effects on hERG channels and predict QTcI intervals in healthy women pretreated with progesterone. Further study into maternal and fetal exposure to these metabolites and potential to prolong cardiac repolarization is warranted., (© 2019, The American College of Clinical Pharmacology.)
- Published
- 2020
- Full Text
- View/download PDF
33. Premature ventricular complexes: diagnostic and therapeutic considerations in clinical practice : A state-of-the-art review by the American College of Cardiology Electrophysiology Council.
- Author
-
Gorenek B, Fisher JD, Kudaiberdieva G, Baranchuk A, Burri H, Campbell KB, Chung MK, Enriquez A, Heidbuchel H, Kutyifa V, Krishnan K, Leclercq C, Ozcan EE, Patton KK, Shen W, Tisdale JE, Turagam MK, and Lakkireddy D
- Subjects
- Diagnosis, Differential, Humans, Ventricular Premature Complexes physiopathology, Ventricular Premature Complexes diagnosis, Ventricular Premature Complexes therapy
- Abstract
Premature ventricular complexes (PVCs) are common arrhythmias in the clinical setting. PVCs in the structurally normal heart are usually benign, but in the presence of structural heart disease (SHD), they may indicate increased risk of sudden death. High PVC burden may induce cardiomyopathy and left ventricular (LV) dysfunction or worsen underlying cardiomyopathy. Sometimes PVCs may be a marker of underlying pathophysiologic process such as myocarditis. Identification of PVC burden is important, since cardiomyopathy and LV dysfunction can reverse after catheter ablation or pharmacological suppression. This state-of-the-art review discusses pathophysiology, clinical manifestations, how to differentiate benign and malignant PVCs, PVCs in the structurally normal heart, underlying SHD, diagnostic procedures (physical examination, electrocardiogram, ambulatory monitoring, exercise testing, echocardiography, cardiac magnetic resonance imaging, coronary angiography, electrophysiology study), and treatment (lifestyle modification, electrolyte imbalance, medical, and catheter ablation).
- Published
- 2020
- Full Text
- View/download PDF
34. Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men: A Randomized, Double-Blind, Placebo-Controlled Crossover-Design Study.
- Author
-
Muensterman ET, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, and Tisdale JE
- Subjects
- Administration, Cutaneous, Administration, Oral, Aged, Aged, 80 and over, Cross-Over Studies, Double-Blind Method, Electrocardiography, Female, Humans, Male, Placebos, Progesterone therapeutic use, Systole physiology, Testosterone therapeutic use, Torsades de Pointes epidemiology
- Published
- 2019
- Full Text
- View/download PDF
35. Proarrhythmic food for thought.
- Author
-
Tisdale JE
- Subjects
- Arrhythmias, Cardiac, Healthy Volunteers, Humans, Citrus paradisi, Long QT Syndrome
- Published
- 2019
- Full Text
- View/download PDF
36. Pharmacists and Cardiologists in the ACC.
- Author
-
Kovacs RJ, Birtcher KK, and Tisdale JE
- Published
- 2019
- Full Text
- View/download PDF
37. Navigating the Minefield of QTc Interval-Prolonging Therapy in Nursing Facility Residents.
- Author
-
Zarowitz BJ and Tisdale JE
- Subjects
- Aged, Humans, Risk Factors, Long QT Syndrome chemically induced, Nursing Homes, Polypharmacy
- Abstract
Background: The exponential increase in the number of medications associated with clinically important prolongation of the heart rate-corrected QT interval (QTc) places older adults at increased risk of arrhythmias including life-threatening torsade de pointes (TdP) and sudden death. Risk factors, other than age older than 65 years and female sex, include multiple concurrent drugs that prolong QTc and a variety of underlying predisposing conditions. Although electronic medical records and pharmacy dispensing systems can alert clinicians to the risk of QTc-prolonging therapy, more than 95% of safety alerts are overridden, and many systems have deactivated QTc drug interaction alerts. The clinical consequences, magnitude of the effect, mitigation strategies, and recommended monitoring are not well defined for nursing facility (NF) residents., Design: Narrative review., Setting: NFs in the United States., Participants: NF residents., Results: Medications known to prolong QTc include selected anti-infectives, antidepressants, urinary anticholinergics, antipsychotics, and cholinesterase inhibitors (eg, donepezil), used commonly in NFs. Drug-drug interactions are a risk when adding a medication that exaggerates the effect or inhibits the metabolism of a QTc-prolonging medication. The vast majority of patients in whom TdP is induced by noncardiac drugs have risk factors that are easily identifiable., Conclusions: Recommendations are provided to improve standardization and use of drug interaction alerts, evaluate the risk of QTc-prolonging drugs in older adults receiving generally lower doses, validate a QTc risk score addressing complex multimorbidity, garner evidence to guide clinical decision making, avail NFs of access to electrocardiograms and interpretive recommendations, and develop standards of practice for hosting risk discussions with residents and their families. J Am Geriatr Soc, 1-8, 2019., (© 2019 The American Geriatrics Society.)
- Published
- 2019
- Full Text
- View/download PDF
38. Editorial commentary: Amiodarone-induced thyroid diseases: Additional unintended consequences.
- Author
-
Tisdale JE
- Subjects
- Humans, Amiodarone, Thyroid Diseases
- Published
- 2019
- Full Text
- View/download PDF
39. Amiodarone for prevention of atrial fibrillation following esophagectomy.
- Author
-
Tisdale JE, Jaynes HA, Watson MR, Corya AL, Shen C, and Kesler KA
- Subjects
- Aged, Amiodarone administration & dosage, Amiodarone adverse effects, Anti-Arrhythmia Agents administration & dosage, Anti-Arrhythmia Agents adverse effects, Atrial Fibrillation etiology, Case-Control Studies, Chemoprevention methods, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Propensity Score, Retrospective Studies, Amiodarone therapeutic use, Anti-Arrhythmia Agents therapeutic use, Atrial Fibrillation prevention & control, Esophagectomy adverse effects
- Abstract
Objectives: Atrial fibrillation (AF) is a common complication after esophagectomy and is associated with symptoms, hemodynamic instability, prolonged hospital stay, and an increased incidence of mortality. Our objective was to determine the efficacy and safety of intravenous amiodarone for prophylaxis of postesophagectomy AF., Methods: In this retrospective cohort study, 309 patients who underwent esophagectomy formed the initial cohort. Following propensity score-matching, 110 patients who received prophylactic amiodarone 43.75 mg/hour via continuous intravenous infusion over 96 hours (total dose, 4200 mg) were matched to a control group of patients who did not undergo amiodarone prophylaxis (n = 110). The propensity score was obtained using a multivariate logistic regression model with amiodarone as the variable and the following covariates: age, sex, surgical approach, history of neoadjuvant chemotherapy and/or radiation, chronic obstructive pulmonary disease, heart failure, cardiovascular disease, alcohol use (>7 drinks/week), preadmission β-blockers discontinued during hospitalization, preoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, preoperative use of corticosteroids, postoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, postoperative use of corticosteroids, postoperative use of statins, and preoperative Charlson comorbidity index., Results: The incidence of AF requiring treatment due to rapid ventricular rate and symptoms was lower in the amiodarone group (17 out of 110 [15.5%] vs 32 out of 110 [29.1%]; odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P = .015). There were no significant differences between the groups in median postoperative length of hospital stay, incidence of pulmonary complications, or mortality. The incidences of hypotension requiring treatment (42.7% vs 21.8%; P = .001), bradycardia (8.2% vs 0.0%; P = .002), and corrected QT interval prolongation (10.9% vs 0.0%; P ≤ .0001) were significantly higher in the amiodarone group., Conclusions: Prophylactic intravenous amiodarone is associated with a reduction in the incidence of AF following esophagectomy, but is not associated with shorter postoperative length of hospital stay. Intravenous amiodarone for prophylaxis of postesophagectomy AF is associated with hypotension, bradycardia, and corrected QT interval prolongation., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
40. Progesterone pretreatment reduces the incidence of drug-induced torsades de pointes in atrioventricular node-ablated isolated perfused rabbit hearts.
- Author
-
Tisdale JE, Jaynes HA, Overholser BR, Sowinski KM, and Kovacs RJ
- Subjects
- Action Potentials drug effects, Animals, Atrioventricular Node physiopathology, Disease Models, Animal, Estradiol blood, Female, Hormone Replacement Therapy, Isolated Heart Preparation, Ovariectomy, Progesterone blood, Rabbits, Time Factors, Torsades de Pointes blood, Torsades de Pointes chemically induced, Torsades de Pointes physiopathology, Atrioventricular Node surgery, Heart Rate drug effects, Phenethylamines, Progesterone pharmacology, Sulfonamides, Torsades de Pointes prevention & control
- Abstract
Introduction: Higher progesterone concentrations are protective against drug-induced prolongation of ventricular repolarization. We tested the hypothesis that pretreatment with progesterone reduces the incidence of drug-induced torsades de pointes (TdP)., Methods and Results: Female New Zealand white rabbits (2.5-3.2 kg) underwent ovariectomy and were randomized to undergo implantation with subcutaneous 21-day sustained release pellets containing progesterone 50 mg (n = 22) or placebo (n = 23). After 20 days, hearts were excised, mounted, and perfused with modified Krebs-Henseleit solution. The atrioventricular (AV) node was destroyed manually. Following a 15-minute equilibration period, hearts were perfused with dofetilide 100 nM for 30 minutes, during which the electrocardiogram was recorded continuously. Incidences of spontaneous TdP, other ventricular arrhythmias and mean QT
c intervals were compared. Median serum progesterone concentrations were higher in progesterone vs placebo-treated rabbits (3.8 [range, 2.8-5.1] vs 0.7 [0.4-1.7] ng/mL, P < 0.0001). Median serum estradiol concentrations were similar (58 [22-72] vs 53 [34-62] pg/mL), P = 0.79). The incidence of TdP was lower in hearts from progesterone-treated rabbits (27% vs 61%, P = 0.049). The incidences of bigeminy (36% vs 74%, P = 0.03) and trigeminy (18% vs 57%, P = 0.01) were also lower in hearts from progesterone-treated rabbits. There was no significant difference between groups in incidence of couplets (59% vs 74%, P = 0.54) or monomorphic ventricular tachycardia (14% vs 30%, P = 0.28). Maximum QTc interval and short-term beat-to-beat QT interval variability during dofetilide perfusion were significantly shorter in hearts from progesterone-treated rabbits., Conclusions: Pretreatment with progesterone reduces the incidence of drug-induced TdP, bigeminy, and trigeminy in isolated perfused AV node-ablated rabbit hearts., (© 2019 Wiley Periodicals, Inc.)- Published
- 2019
- Full Text
- View/download PDF
41. Predictive Analytics for Identification of Patients at Risk for QT Interval Prolongation: A Systematic Review.
- Author
-
Tomaselli Muensterman E and Tisdale JE
- Subjects
- Humans, Long QT Syndrome chemically induced, Risk Factors, Long QT Syndrome prevention & control, Models, Statistical, Risk Assessment statistics & numerical data
- Abstract
Prolongation of the heart rate-corrected QT (QTc) interval increases the risk for torsade de pointes (TdP), a potentially fatal arrhythmia. The likelihood of TdP is higher in patients with risk factors that include female sex, older age, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, concomitant administration of two or more QTc interval-prolonging medications, among others. Assessment and quantification of risk factors may facilitate prediction of patients at highest risk for developing QTc interval prolongation and TdP. Investigators have utilized the field of predictive analytics, which generates predictions using techniques including data mining, modeling, machine learning, and others, to develop methods of risk quantification and prediction of QTc interval prolongation. Predictive analytics have also been incorporated into clinical decision support (CDS) tools to alert clinicians regarding patients at increased risk of developing QTc interval prolongation. The objectives of this article are to assess the effectiveness of predictive analytics for identification of patients at risk of drug-induced QTc interval prolongation and to discuss the efficacy of incorporation of predictive analytics into CDS tools in clinical practice. A systematic review of English-language articles (human subjects only) was performed, yielding 57 articles, with an additional 4 articles identified from other sources; a total of 10 articles were included in this review. Risk scores for QTc interval prolongation have been developed in various patient populations including those in cardiac intensive care units (ICUs) and in broader populations of hospitalized or health system patients. One group developed a risk score that includes information regarding genetic polymorphisms; this score significantly predicted TdP. Development of QTc interval prolongation risk prediction models and incorporation of these models into CDS tools reduce the risk of QTc interval prolongation in cardiac ICUs and identify health system patients at increased risk for mortality. The impact of these QTc interval prolongation predictive analytics on overall patient safety outcomes, such as TdP and sudden cardiac death relative to the cost of development and implementation, requires further study., (© 2018 Pharmacotherapy Publications, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
42. Ondansetron blocks wild-type and p.F503L variant small-conductance Ca 2+ -activated K + channels.
- Author
-
Ko JS, Guo S, Hassel J, Celestino-Soper P, Lynnes TC, Tisdale JE, Zheng JJ, Taylor SE, Foroud T, Murray MD, Kovacs RJ, Li X, Lin SF, Chen Z, Vatta M, Chen PS, and Rubart M
- Subjects
- Animals, Anti-Arrhythmia Agents therapeutic use, Calcium metabolism, Cells, Cultured, Female, HEK293 Cells, Humans, Long QT Syndrome genetics, Mice, Mice, Inbred C57BL, Middle Aged, Mutation, Missense, Ondansetron therapeutic use, Potassium Channel Blockers therapeutic use, Small-Conductance Calcium-Activated Potassium Channels genetics, Small-Conductance Calcium-Activated Potassium Channels metabolism, Anti-Arrhythmia Agents pharmacology, Long QT Syndrome drug therapy, Ondansetron pharmacology, Potassium Channel Blockers pharmacology, Small-Conductance Calcium-Activated Potassium Channels antagonists & inhibitors
- Abstract
Apamin-sensitive small-conductance Ca
2+ -activated K+ (SK) current ( IKAS ) is encoded by Ca2+ -activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS . We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+ -activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.- Published
- 2018
- Full Text
- View/download PDF
43. Research Conducted by Hospital Pharmacists: Integral Component of Daily Practice or Unrealistic Expectation?
- Author
-
Tisdale JE
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2018
44. La recherche réalisée par les pharmaciens d’hôpitaux : une composante indispensable de la pratique quotidienne ou une attente irréaliste?
- Author
-
Tisdale JE
- Abstract
Competing Interests: Intérêts concurrents : Aucun déclaré.
- Published
- 2018
45. Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study.
- Author
-
Alburikan KA, Aldemerdash A, Savitz ST, Tisdale JE, Whitsel EA, Soliman EZ, Thudium EM, Sueta CA, Kucharska-Newton AM, Stearns SC, and Rodgers JE
- Subjects
- Age Factors, Aged, Blood Pressure, Body Weights and Measures, Comorbidity, Female, Humans, Hypertrophy, Left Ventricular epidemiology, Male, Middle Aged, Risk Assessment, Risk Factors, Sex Factors, Atherosclerosis epidemiology, Electrocardiography, Long QT Syndrome chemically induced, Long QT Syndrome epidemiology
- Abstract
Rationale, Aims, and Objectives: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening., Method: The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ≥ 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ≥ 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person., Results: Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone., Conclusion: Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors., (© 2017 John Wiley & Sons, Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
46. Editorial Commentary: Optimization of dose selection for nonvitamin K antagonist oral anticoagulants.
- Author
-
Tisdale JE
- Subjects
- Administration, Oral, Atrial Fibrillation, Humans, Stroke, Anticoagulants, Vitamin K
- Published
- 2017
- Full Text
- View/download PDF
47. Prevalence and significance of acquired QT interval prolongation in hospitalized patients.
- Author
-
Tisdale JE
- Subjects
- Arrhythmias, Cardiac, Electrocardiography, Humans, Prevalence, Long QT Syndrome epidemiology, Torsades de Pointes epidemiology
- Published
- 2017
- Full Text
- View/download PDF
48. Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.
- Author
-
Tisdale JE, Jaynes HA, Overholser BR, Sowinski KM, Flockhart DA, and Kovacs RJ
- Abstract
Objectives: We tested the hypothesis that oral progesterone administration attenuates drug-induced QT interval lengthening., Background: Evidence from preclinical and human investigations suggests that higher serum progesterone concentrations may be protective against drug-induced QT interval lengthening., Methods: In this prospective, double-blind, crossover study, 19 healthy female volunteers (21-40 years) were randomized to receive progesterone 400 mg or matching placebo orally once daily for 7 days timed to the menses phase of the menstrual cycle (between-phase washout period = 49 days). On day 7, ibutilide 0.003 mg/kg was infused over 10 minutes, after which QT intervals were recorded and blood samples collected for 12 hours. Prior to the treatment phases, subjects underwent ECG monitoring for 12 hours to calculate individualized heart rate-corrected QT intervals (QT
c I)., Results: Fifteen subjects completed all study phases. Maximum serum ibutilide concentrations in the progesterone and placebo phases were similar (1247±770 vs 1172±709 pg/mL, p=0.43). Serum progesterone concentrations were higher during the progesterone phase (16.2±11.0 vs 1.2±1.0 ng/mL, p<0.0001), while serum estradiol concentrations in the two phases were similar (89.3±62.8 vs 71.8±31.7 pg/mL, p=0.36). Pre-ibutilide lead II QTc I was significantly lower in the progesterone phase (412±15 vs 419±14 ms, p=0.04). Maximum ibutilide-associated QTc I (443±17 vs 458±19 ms, p=0.003), maximum percent increase in QTc I from pretreatment value (7.5±2.4 vs 9.3±3.4%, p=0.02) and area under the effect (QTc I) curve during the first hour post-ibutilide (497±13 vs 510±16 ms-hr, p=0.002) were lower during the progesterone phase. Progesterone-associated adverse effects included fatigue/malaise and vertigo., Conclusions: Oral progesterone administration attenuates drug-induced QTc I lengthening.- Published
- 2016
- Full Text
- View/download PDF
49. Iterative Development and Evaluation of a Pharmacogenomic-Guided Clinical Decision Support System for Warfarin Dosing.
- Author
-
Melton BL, Zillich AJ, Saleem J, Russ AL, Tisdale JE, and Overholser BR
- Subjects
- Drug Prescriptions, Female, Humans, Male, Warfarin pharmacology, Decision Support Systems, Clinical, Drug Dosage Calculations, Pharmacogenetics, Warfarin therapeutic use
- Abstract
Objective: Pharmacogenomic-guided dosing has the potential to improve patient outcomes but its implementation has been met with clinical challenges. Our objective was to develop and evaluate a clinical decision support system (CDSS) for pharmacogenomic-guided warfarin dosing designed for physicians and pharmacists., Methods: Twelve physicians and pharmacists completed 6 prescribing tasks using simulated patient scenarios in two iterations (development and validation phases) of a newly developed pharmacogenomic-driven CDSS prototype. For each scenario, usability was measured via efficiency, recorded as time to task completion, and participants' perceived satisfaction which were compared using Kruskal-Wallis and Mann Whitney U tests, respectively. Debrief interviews were conducted and qualitatively analyzed. Usability findings from the first (i.e. development) iteration were incorporated into the CDSS design for the second (i.e. validation) iteration., Results: During the CDSS validation iteration, participants took more time to complete tasks with a median (IQR) of 183 (124-247) seconds versus 101 (73.5-197) seconds in the development iteration (p=0.01). This increase in time on task was due to the increase in time spent in the CDSS corresponding to several design changes. Efficiency differences that were observed between pharmacists and physicians in the development iteration were eliminated in the validation iteration. The increased use of the CDSS corresponded to a greater acceptance of CDSS recommended doses in the validation iteration (4% in the first iteration vs. 37.5% in the second iteration, p<0.001). Overall satisfaction did not change statistically between the iterations but the qualitative analysis revealed greater trust in the second prototype., Conclusions: A pharmacogenomic-guided CDSS has been developed using warfarin as the test drug. The final CDSS prototype was trusted by prescribers and significantly increased the time using the tool and acceptance of the recommended doses. This study is an important step toward incorporating pharmacogenomics into CDSS design for clinical testing.
- Published
- 2016
- Full Text
- View/download PDF
50. Efavirenz Inhibits the Human Ether-A-Go-Go Related Current (hERG) and Induces QT Interval Prolongation in CYP2B6*6*6 Allele Carriers.
- Author
-
Abdelhady AM, Shugg T, Thong N, Lu JB, Kreutz Y, Jaynes HA, Robarge JD, Tisdale JE, Desta Z, and Overholser BR
- Subjects
- Action Potentials, Adolescent, Adult, Alkynes, Benzoxazines blood, Cyclopropanes, Cytochrome P-450 CYP2B6 metabolism, Dose-Response Relationship, Drug, ERG1 Potassium Channel metabolism, Electrocardiography, Female, Gene Frequency, Genotype, HEK293 Cells, Healthy Volunteers, Heart Rate drug effects, Homozygote, Humans, Male, Pharmacogenetics, Phenotype, Potassium Channel Blockers blood, Reverse Transcriptase Inhibitors blood, Risk Assessment, Risk Factors, Time Factors, Torsades de Pointes genetics, Torsades de Pointes metabolism, Torsades de Pointes physiopathology, Transfection, Young Adult, Benzoxazines adverse effects, Cytochrome P-450 CYP2B6 genetics, ERG1 Potassium Channel antagonists & inhibitors, Pharmacogenomic Variants, Potassium Channel Blockers adverse effects, Reverse Transcriptase Inhibitors adverse effects, Torsades de Pointes chemically induced
- Abstract
Background: Efavirenz (EFV) has been associated with torsade de pointes despite marginal QT interval lengthening. Since EFV is metabolized by the cytochrome P450 (CYP) 2B6 enzyme, we hypothesized that EFV would lengthen the rate-corrected QT (QTcF) interval in carriers of the CYP2B6*6 decreased functional allele., Objective: The primary objective of this study was to evaluate EFV-associated QT interval changes with regard to CYP2B6 genotype and to explore mechanisms of QT interval lengthening., Methods: EFV was administered to healthy volunteers (n = 57) as a single 600 mg dose followed by multiple doses to steady-state. Subjects were genotyped for known CYP2B6 alleles and ECGs and EFV plasma concentrations were obtained serially. Whole-cell, voltage-clamp experiments were performed on cells stably expressing hERG and exposed to EFV in the presence and absence of CYP2B6 expression., Results: EFV demonstrated a gene-dose effect and exceeded the FDA criteria for QTcF interval prolongation in CYP2B6*6/*6 carriers. The largest mean time-matched differences ∆∆QTcF were observed at 6 hours (14 milliseconds; 95% CI [1; 27]), 12 hours (18 milliseconds; 95% CI [-4; 40]), and 18 hours (6 milliseconds; 95% CI [-1; 14]) in the CYP2B6*6/*6 genotype. EFV concentrations exceeding 0.4 μg/mL significantly inhibited outward hERG tail currents (P < 0.05)., Conclusions: This study demonstrates that homozygous carriers of CYP2B6*6 allele may be at increased risk for EFV-induced QTcF interval prolongation via inhibition of hERG., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.