Browsing by Author "Kovacs, Richard J."

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    A Rare Case of Transient Inferior ST Segment Elevation
    (Wolters Kluwer, 2013) Basir, Babar; Safadi, Bilal; Kovacs, Richard J.; Tahir, Bilal; Medicine, School of Medicine
    The investigators review the electrocardiographic manifestations of hiatal hernia and describe the case of an 86-year-old male who presented with a large distended hiatal hernia causing electrocardiographic findings of new onset ST segment elevation of the inferior leads without reciprocal changes. After decompression, the patient's electrocardiogram demonstrated resolution of the ST segment elevation.
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    Arrhythmias in Patients With Heart Failure Prescribed Dofetilide or Sotalol
    (Elsevier, 2024-11-07) Huang, Chien-Yu; Overholser, Brian R.; Sowinski, Kevin M.; Jaynes, Heather A.; Kovacs, Richard J.; Tisdale, James E.; Medicine, School of Medicine
    Background: Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced arrhythmias. It is unknown whether HF with preserved ejection fraction (HFpEF) also increases the risk. Objectives: The purpose of this study was to determine if the risk of ventricular tachycardia (VT) and sudden cardiac arrest (SCA) is increased in patients with HFpEF prescribed dofetilide or sotalol. Methods: Using Medicare claims and pharmacy benefits from 2014 to 2016, we identified patients taking dofetilide or sotalol and non-dofetilide/sotalol users among 3 groups: HFrEF (n = 26,176), HFpEF (n = 33,304), and no HF (n = 580,249). Multinomial propensity score matching was performed. We compared baseline characteristics using Cochran-Mantel-Haenszel statistics and standardized differences, and tested associations of VT and SCA among dofetilide/sotalol users and those with HFpEF, HFrEF, or no HF using a generalized Cox proportional hazards model. Results: VT and SCA occurred 166 (10.68%) and 16 (1.03%) of 1,554 dofetilide/sotalol users with HFpEF, 543 (38.76%) and 40 (2.86%) of 1,401 dofetilide/sotalol users with HFrEF, and 245 (5.06%) and 13 (0.27%) of 4,839 dofetilide/sotalol users without HF. Overall VT risk was increased in HFrEF and HFpEF patients (HR: 7.00 [95% CI: 6.10-8.02] and 1.99 [95% CI: 1.70-2.32], respectively). The risk of VT in patients prescribed dofetilide/sotalol was increased in HFrEF and HFpEF patients (1.53 [95% CI: 1.07-2.20] and 2.34 [95% CI: 1.11-4.95], respectively). While the overall SCA risk was increased in HFrEF and HFpEF patients (5.19 [95% CI: 4.10-6.57] and 2.53 [95% CI: 1.98-3.23], respectively), dofetilide/sotalol use was not associated with an increased SCA risk. Conclusions: In patients with HF who are prescribed dofetilide or sotalol, the risk of VT, but not SCA, was increased.
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    Athlete ECG T-wave abnormality interpretation patterns by non-experts
    (Elsevier, 2022-05) Torabi, Asad J.; Nahhas, Omar D.; Dunn, Reginald E.; Martinez, Matthew W.; Tucker, Andrew M.; Lincoln, Andrew E.; Kovacs, Richard J.; Emery, Michael S.; Medicine, School of Medicine
    Background The presence of T-wave abnormalities (TWA) on an athlete's electrocardiogram (ECG) presents as a diagnostic challenge for physicians. Types of TWA patterns classified as abnormal by inexperienced readers have not been systematically analyzed. Methods ECGs from the 2011–2015 National Football League Scouting Combine (initially interpreted by general cardiologists) were retrospectively reviewed by expert sports cardiologists with strict application of the 2017 International Criteria. Patterns of TWA that were altered from the original interpretation were analyzed. Results The study included 1643 athletes (mean age 22 years). There was a 67 % reduction in the number of athletes with any TWA (p < 0.001) with 111 ECGs changed to normal. Inferior TWA was the most common interpreted initial ECG abnormality altered followed by anterior and lateral. Discussion This analysis revealed an initial high rate of TWA by non-expert readers. Tailored education programs to physicians who interpret athlete ECGs should highlight these specific T-wave patterns. We see this as an opportunity to make more clinicians aware of ECG interpretation guidelines as sports trained cardiologists are mostly self-taught.
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    Athlete ECG T-wave abnormality interpretation patterns by non-experts
    (Elsevier, 2022-06-16) Torabi, Asad J.; Nahhas, Omar D.; Dunn, Reginald E.; Martinez, Matthew W.; Tucker, Andrew M.; Lincoln, Andrew E.; Kovacs, Richard J.; Emery, Michael S.; Graduate Medical Education, School of Medicine
    Background: The presence of T-wave abnormalities (TWA) on an athlete's electrocardiogram (ECG) presents as a diagnostic challenge for physicians. Types of TWA patterns classified as abnormal by inexperienced readers have not been systematically analyzed. Methods: ECGs from the 2011-2015 National Football League Scouting Combine (initially interpreted by general cardiologists) were retrospectively reviewed by expert sports cardiologists with strict application of the 2017 International Criteria. Patterns of TWA that were altered from the original interpretation were analyzed. Results: The study included 1643 athletes (mean age 22 years). There was a 67 % reduction in the number of athletes with any TWA (p < 0.001) with 111 ECGs changed to normal. Inferior TWA was the most common interpreted initial ECG abnormality altered followed by anterior and lateral. Discussion: This analysis revealed an initial high rate of TWA by non-expert readers. Tailored education programs to physicians who interpret athlete ECGs should highlight these specific T-wave patterns. We see this as an opportunity to make more clinicians aware of ECG interpretation guidelines as sports trained cardiologists are mostly self-taught.
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    Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study
    (Springer US, 2015-10) Kovacs, Richard J.; Maldonado, Giuliana; Azaro, Analia; Fernández, Maria S.; Romero, Federico L.; Sepulveda-Sánchez, Juan M.; Corretti, Mary; Carducci, Michael; Dolan, Melda; Gueorguieva, Ivelina; Cleverly, Ann L.; Pillay, N. Sokalingum; Baselga, Jose; Lahn, Michael M.; Department of Medicine, IU School of Medicine
    Transforming growth factor-beta (TGF-β) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-β signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-β inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or in combination with lomustine (n = 26). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2 months, monthly electrocardiograms, thorax computer tomography scans every 6 months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ≥6 months (n = 13). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-β inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials.
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    Effect of Modernized Collaborative Care for Depression on Depressive Symptoms and Cardiovascular Disease Risk Biomarkers: eIMPACT Randomized Controlled Trial
    (Elsevier, 2023) Stewart, Jesse C.; Patel, Jay S.; Polanka, Brittanny M.; Gao, Sujuan; Nurnberger, John I., Jr.; MacDonald, Krysha L.; Gupta, Samir K.; Considine, Robert V.; Kovacs, Richard J.; Vrany, Elizabeth A.; Berntson, Jessica; Hsueh, Loretta; Shell, Aubrey L.; Rollman, Bruce L.; Callahan, Christopher M.; Psychology, School of Science
    Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges' g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results - 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93-7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers - i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, β-thromboglobulin, and platelet factor 4 (Hedges' gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention - which harnessed technology to maximize access and minimize resources - produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches.
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    Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men
    (American Heart Association, 2019-09-23) Muensterman, Elena Tomaselli; Jaynes, Heather A.; Sowinski, Kevin M.; Overholser, Brian R.; Shen, Changyu; Kovacs, Richard J.; Tisdale, James E.; Medicine, School of Medicine
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    Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients
    (Ovid Technologies Wolters Kluwer - American Heart Association, 2014-05) Tisdale, James E.; Jaynes, Heather A.; Kingery, Joanna R.; Overholser, Brian R.; Mourad, Noha A.; Trujillo, Tate N.; Kovacs, Richard J.; Department of Medicine, IU School of Medicine
    BACKGROUND: We evaluated the effectiveness of a computer clinical decision support system (CDSS) for reducing the risk of QT interval prolongation in hospitalized patients. METHODS AND RESULTS: We evaluated 2400 patients admitted to cardiac care units at an urban academic medical center. A CDSS incorporating a validated risk score for QTc prolongation was developed and implemented using information extracted from patients' electronic medical records. When a drug associated with torsades de pointes was prescribed to a patient at moderate or high risk for QTc interval prolongation, a computer alert appeared on the screen to the pharmacist entering the order, who could then consult the prescriber on alternative therapies and implement more intensive monitoring. QTc interval prolongation was defined as QTc interval >500 ms or increase in QTc of ≥60 ms from baseline; for patients who presented with QTc >500 ms, QTc prolongation was defined solely as increase in QTc ≥60 ms from baseline. End points were assessed before (n=1200) and after (n=1200) implementation of the CDSS. CDSS implementation was independently associated with a reduced risk of QTc prolongation (adjusted odds ratio, 0.65; 95% confidence interval, 0.56-0.89; P<0.0001). Furthermore, CDSS implementation reduced the prescribing of noncardiac medications known to cause torsades de pointes, including fluoroquinolones and intravenous haloperidol (adjusted odds ratio, 0.79; 95% confidence interval, 0.63-0.91; P=0.03). CONCLUSIONS: A computer CDSS incorporating a validated risk score for QTc prolongation influences the prescribing of QT-prolonging drugs and reduces the risk of QTc interval prolongation in hospitalized patients with torsades de pointes risk factors.
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    Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction
    (Elsevier, 2020-09) Tisdale, James E.; Jaynes, Heather A.; Overholser, Brian R.; Sowinski, Kevin M.; Fisch, Mark D.; Rodgers, Jo E.; Aldemerdash, Ahmed; Hsu, Chia-Chi; Wang, Nan; Tomaselli Muensterman, Elena; Rao, Vijay U.; Kovacs, Richard J.; Medicine, School of Medicine
    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 (QTF) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTFvs 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.
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    Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study
    (Elsevier, 2016-12) Tisdale, James E.; Jaynes, Heather A.; Overholser, Brian R.; Sowinski, Kevin M.; Flockhart, David A.; Kovacs, Richard J.; Medicine, School of Medicine
    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 (QTcI). 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 QTcI was significantly lower in the progesterone phase (412±15 vs 419±14 ms, p=0.04). Maximum ibutilide-associated QTcI (443±17 vs 458±19 ms, p=0.003), maximum percent increase in QTcI from pretreatment value (7.5±2.4 vs 9.3±3.4%, p=0.02) and area under the effect (QTcI) 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 QTcI lengthening.