Craig Heise

Interests

Research

Decision support, drug induced arrhythmias, interactive teaching, medical toxicology

Teaching

Interactive learning, medical toxicology, precision medicine

Courses

No activities entered.

Scholarly Contributions

Chapters

• Brooks, D. E., & Heise, C. W. (2017). Anxiolytics, Sedatives, and Hypnotics. In Goldfranks Medical Toxicology. Springer International Publishing. doi:10.1007/978-3-319-17900-1_35
• Brooks, D. E., & Heise, C. W. (2015). Anxiolytic/Sedative-Hypnotics. In Goldfranks Medical Toxicology. Springer International Publishing. doi:10.1007/978-3-319-20790-2_35-1
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  Tox gold standard textbook chapter

Journals/Publications

• Gallo, T., Curry, S. C., Heise, C. W., Antonescu, C. C., & Raschke, R. A. (2023). Clinical decision support to reduce unnecessary diagnostic testing for heparin-induced thrombocytopenia. British journal of haematology, 202(5), 1011-1017.
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  Appropriate evaluation of heparin-induced thrombocytopenia (HIT) is imperative because of the potentially life-threatening complications. However, overtesting and overdiagnosis of HIT are common. Our goal was to evaluate the impact of clinical decision support (CDS) based on the HIT computerized-risk (HIT-CR) score, designed to reduce unnecessary diagnostic testing. This retrospective observational study evaluated CDS that presented a platelet count versus time graph and 4Ts score calculator to clinicians who initiated a HIT immunoassay order in patients with predicted low risk (HIT-CR score 0-2). The primary outcome was the proportion of immunoassay orders initiated but cancelled after firing of the CDS advisory. Chart reviews were conducted to assess anticoagulation usage, 4Ts scores and the proportion of patients who had HIT. In a 20-week period, 319 CDS advisories were presented to users who initiated potentially unnecessary HIT diagnostic testing. The diagnostic test order was discontinued in 80 (25%) patients. Heparin products were continued in 139 (44%) patients, and alternative anticoagulation was not given to 264 (83%). The negative predictive value of the advisory was 98.8% (95% CI: 97.2-99.5). HIT-CR score-based CDS can reduce unnecessary diagnostic testing for HIT in patients with a low pretest probability of HIT.
• Gallo, T., Curry, S. C., Heise, C. W., Antonescu, C. C., & Raschke, R. A. (2023). Clinical decision support to reduce unnecessary diagnostic testing for heparin‐induced thrombocytopenia. British Journal of Haematology, 202(5), 1011-1017. doi:10.1111/bjh.18902
• Gallo, T., Heise, C., Woosely, R., Tisdale, J., Antonescu, C., Gephart, S. M., & Malone, D. C. (2021). Clinician satisfaction with advanced clinical decision support to reduce the risk of torsades de pointes. Applied Clinical Informatics.
• Maghari, S., Gallo, T., Rivas, S., German, A., Nguyen Le, M. Q., Abbaszadegan, H., Zubriski, M. A., Heise, C. W., & Landas, N. D. (2023). Prescription medications with actionable pharmacogenomic recommendations in Veterans Health Administration patients. Pharmacogenomics, 24(9), 501-508.
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  To evaluate the prevalence of medications with actionable pharmacogenomic (PGx) safety and efficacy recommendations in patients receiving care from the Veterans Health Administration. Outpatient prescription data from 2011 to 2021 and any documented adverse drug reactions (ADRs) were reviewed for those who received PGx testing at one Veterans Administration location between November 2019 and October 2021. Among the reviewed prescriptions, 381 (32.8%) were associated with an actionable recommendation based on the Clinical Pharmacogenetics Implementation Consortium (CPIC) prescribing guidelines, with 205 (17.7%) for efficacy concerns and 176 (15.2%) for safety concerns. Among those with a documented ADR for a PGx-impacted medication, 39.1% had PGx results that aligned with CPIC recommendations. Medications with actionable PGx recommendations for safety and efficacy concerns are received with similar frequency, and most patients who have undergone PGx testing at the Phoenix Veterans Administration have received medications that may be impacted by PGx testing.
• Maghari, S., Gallo, T., Rivas, S., German, A., Nguyen Le, M. Q., Abbaszadegan, H., Zubriski, M. A., Heise, C. W., & Landas, N. D. (2023). Prescription medications with actionable pharmacogenomic recommendations in Veterans Health Administration patients. Pharmacogenomics, 24(9), 501-508. doi:10.2217/pgs-2023-0018
• Tan, M. S., Heise, C. W., Gallo, T., Tisdale, J. E., Woosley, R. L., Antonescu, C. C., Gephart, S. M., & Malone, D. C. (2023). Relationship between a risk score for QT interval prolongation and mortality across rural and urban inpatient facilities. Journal of electrocardiology, 77, 4-9.
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  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).
• Gallo, T., Heise, C. W., Woosley, R. L., Tisdale, J. E., Tan, M. S., Gephart, S. M., Antonescu, C. C., & Malone, D. C. (2022). Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes. Journal of the American Heart Association, 11(11), e024338.
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  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 (
• Malone, D. C., Malone, D. C., Gephart, S. M., Gephart, S. M., Antonescu, C. C., Antonescu, C. C., Tisdale, J. E., Tisdale, J. E., Woosley, R. L., Woosley, R. L., Heise, C. W., Heise, C. W., Gallo, T., Gallo, T., Gallo, T., Heise, C. W., Woosley, R. L., Tisdale, J. E., Antonescu, C. C., , Gephart, S. M., et al. (2022). Clinician Satisfaction With Advanced Clinical Decision Support to Reduce the Risk of Torsades de Pointes.. Journal of patient safety, 18(6), e1010-e1013. doi:10.1097/pts.0000000000000996
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  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..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..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..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.
• Raschke, R. A., Rangan, P., Agarwal, S., Uppalapu, S., Sher, N., Curry, S. C., & Heise, C. W. (2022). COVID-19 Time of Intubation Mortality Evaluation (C-TIME): A system for predicting mortality of patients with COVID-19 pneumonia at the time they require mechanical ventilation. PloS one, 17(7), e0270193.
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  An accurate system to predict mortality in patients requiring intubation for COVID-19 could help to inform consent, frame family expectations and assist end-of-life decisions.
• Woosley, R. L., Gallo, T., Heise, C. W., Heise, C. W., Gallo, T., Woosley, R. L., Tisdale, J. E., Tisdale, J. E., Tan, M. S., Tan, M. S., Gephart, S. M., Antonescu, C. C., Antonescu, C. C., Gephart, S. M., Malone, D. C., & Malone, D. C. (2022). Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes. Journal of the American Heart Association, 11(11). doi:10.1161/jaha.122.024338
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  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
• Woosley, R. L., Tisdale, J. E., Malone, D. C., Heise, C. W., Gephart, S. M., Gallo, T., & Antonescu, C. C. (2022). Clinician Satisfaction With Advanced Clinical Decision Support to Reduce the Risk of Torsades de Pointes.. Journal of patient safety, Publish Ahead of Print. doi:10.1097/pts.0000000000000996
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  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..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..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..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.
• Dong, O. M., Roberts, M. C., Wu, R. R., Voils, C. I., Sperber, N., Gavin, K. L., Bates, J., Chanfreau-Coffinier, C., Naglich, M., Kelley, M. J., Vassy, J. L., Sriram, P., Heise, C. W., Rivas, S., Ribeiro, M., Chapman, J. G., & Voora, D. (2021). Evaluation of the Veterans Affairs Pharmacogenomic Testing for Veterans (PHASER) clinical program at initial test sites. Pharmacogenomics, 22(17), 1121-1133.
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  The first Plan-Do-Study-Act cycle for the Veterans Affairs Pharmacogenomic Testing for Veterans pharmacogenomic clinical testing program is described. Surveys evaluating implementation resources and processes were distributed to implementation teams, providers, laboratory and health informatics staff. Survey responses were mapped to the Consolidated Framework for Implementation Research constructs to identify implementation barriers. The Expert Recommendation for Implementing Change strategies were used to address implementation barriers. Survey response rate was 23-73% across personnel groups at six Veterans Affairs sites. Nine Consolidated Framework for Implementation Research constructs were most salient implementation barriers. Program revisions addressed these barriers using the Expert Recommendation for Implementing Change strategies related to three domains. Beyond providing free pharmacogenomic testing, additional implementation barriers need to be addressed for improved program uptake.
• Dong, O. M., Roberts, M. C., Wu, R. R., Voils, C. I., Sperber, N., Gavin, K. L., Bates, J., Chanfreau-Coffinier, C., Naglich, M., Kelley, M. J., Vassy, J. L., Sriram, P., Heise, C. W., Rivas, S., Ribeiro, M., Chapman, J. G., & Voora, D. (2021). Evaluation of the Veterans Affairs Pharmacogenomic Testing for Veterans (PHASER) clinical program at initial test sites. Pharmacogenomics, 22(17), 1121-1133. doi:10.2217/pgs-2021-0089
• Gephart, S., Woosley, R. L., Gallo, T., Heise, C. W., Tisdale, J. E., Tan, M., Antonescu, C., & Malone, D. (2021). Abstract 12172: Relationship Between Increased QTc Risk Score and In-Hospital Mortality. Circulation, 144(Suppl_1). doi:10.1161/circ.144.suppl_1.12172
• Raschke, R. A., Agarwal, S., Rangan, P., Heise, C. W., & Curry, S. C. (2021). Discriminant Accuracy of the SOFA Score for Determining the Probable Mortality of Patients With COVID-19 Pneumonia Requiring Mechanical Ventilation. JAMA, 325(14), 1469-1470.
• Raschke, R. A., Agarwal, S., Rangan, P., Heise, C. W., & Curry, S. C. (2021). Discriminant Accuracy of the SOFA Score for Determining the Probable Mortality of Patients With COVID-19 Pneumonia Requiring Mechanical Ventilation. JAMA, 325(14), 1469. doi:10.1001/jama.2021.1545
• Raschke, R. A., Stoffer, B., Assar, S., Fountain, S., Olsen, K., Heise, C. W., Gallo, T., Padilla-Jones, A., Gerkin, R., Parthasarathy, S., & Curry, S. C. (2021). The relationship of tidal volume and driving pressure with mortality in hypoxic patients receiving mechanical ventilation. PloS one, 16(8), e0255812.
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  To determine whether tidal volume/predicted body weight (TV/PBW) or driving pressure (DP) are associated with mortality in a heterogeneous population of hypoxic mechanically ventilated patients.
• Voora, D., Vassy, J. L., Sriram, P., Rozelle, S., Rivas, S., Ribeiro, M., Naglich, M., Meyer, L. J., Kelley, M. J., Jacobitz, R., Icardi, M., Heise, C. W., Dong, O. M., Chapman, J. G., Chanfreau-coffinier, C., Bates, J. S., Voora, D., Vassy, J. L., Sriram, P., , Rozelle, S., et al. (2021). Veterans Affairs Pharmacogenomic Testing for Veterans (PHASER) clinical program.. Pharmacogenomics, 22(3), 137-144. doi:10.2217/pgs-2020-0173
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  In 2019, the Veterans Affairs (VA), the largest integrated US healthcare system, started the Pharmacogenomic Testing for Veterans (PHASER) clinical program that provides multi-gene pharmacogenomic (PGx) testing for up to 250,000 veterans at approximately 50 sites. PHASER is staggering program initiation at sites over a 5-year period from 2019 to 2023, as opposed to simultaneous initiation at all sites, to facilitate iterative program quality improvements through Plan-Do-Study-Act cycles. Current resources in the PGx field have not focused on multisite, remote implementation of panel-based PGx testing. In addition to bringing large scale PGx testing to veterans, the PHASER program is developing a roadmap to maximize uptake and optimize the use of PGx to improve drug response outcomes.
• Heise, C. W., Gallo, T., Curry, S. C., & Woosley, R. L. (2020). Identification of populations likely to benefit from pharmacogenomic testing.. Pharmacogenetics and genomics, 30(5), 91-95. doi:10.1097/fpc.0000000000000400
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  Pharmacogenomic testing (PGX) implementation is rapidly expanding, including pre-emptive testing funded by health systems. PGX continues to develop an evidence base that it saves money and improves clinical outcomes. Identifying the potential impact of pre-emptive testing in specific populations may aid in the development of a business case..We utilized a software tool that can evaluate patient drug lists and identified groups of patients most likely to benefit from implementation of a PGX testing program in a major medical system population..Medication lists were obtained for sixteen patient groups with a total of 82 613 patients. The percent of patients in each group with testing 'Recommended', 'Strongly recommended', or 'Required' ranged from 12.7% in the outpatient pediatric psychiatry group to 75.7% in the any adult inpatient age >50 years group. Some of the highest yield drugs identified were citalopram, simvastatin, escitalopram, metoprolol, clopidogrel, tramadol, and ondansetron..We demonstrate a significant number of patients in each group may have benefit, but targeting certain ones for pre-emptive testing may result in the initial highest yield for a health system.
• Ruha, A., O'connor, A. D., Heise, C. W., Cunningham, C. A., Ruha, A., O'connor, A. D., Heise, C. W., & Cunningham, C. A. (2020). One Bite, Two Patients: Disparate Clinical Courses Following Simultaneous Crotalus oreganus abyssus Envenomation.. Wilderness & environmental medicine, 31(3), 354-357. doi:10.1016/j.wem.2020.05.004
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  A number of crotaline species have been associated with neurotoxic envenomation in North America. One clinical sign that can occur is myokymia: fine, involuntary, wave-like muscle movements occurring at regular intervals. We report an unusual scenario in which a single snakebite resulted in simultaneous envenomation of 2 patients. Both developed myokymia, with 1 having respiratory compromise. One patient also developed a hypersensitivity reaction to antivenom. Envenomation by the Grand Canyon rattlesnake, Crotalus oreganus abyssus, can produce significant neurotoxicity and resultant respiratory compromise. Antivenom may be helpful but can produce hypersensitivity reactions.
• Wang-rodriguez, J., Voora, D., Voils, C. I., Vassy, J. L., Stone, A., Schichman, S. A., Scheuner, M. T., Przygodzki, R. M., Pratt, V. M., Hull, L. E., Heise, C. W., Chanfreau-coffinier, C. C., Wang-rodriguez, J., Heise, C. W., Wang-rodriguez, J., Voora, D., Voils, C. I., Vassy, J. L., Stone, A., , Schichman, S. A., et al. (2020). Identifying End Users' Preferences about Structuring Pharmacogenetic Test Orders in an Electronic Health Record System.. The Journal of molecular diagnostics : JMD, 22(10), 1264-1271. doi:10.1016/j.jmoldx.2020.06.015
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  Pharmacogenetics (PGx) testing can be used for detecting genetic variations that may affect an individual's anticipated metabolism of, or response to, medications. Although several studies have focused on developing tools for delivering results from PGx testing, there is a relative dearth of information about how to design provider-friendly electronic order-entry systems for PGx. The U.S. Department of Veterans Affairs (VA) is preparing to implement a new electronic health records system. In this study, VA PGx test end users were surveyed about their preferences for how electronic test orders for PGx should be structured, including the nomenclature that should be used to search for and identify PGx-test orders, whether to offer single- versus multigene tests, and whether information about test methodology should be included in the order name. Responses were analyzed systematically to identify areas of agreement and disagreement with the survey options, and areas where respondents' opinions diverged. End users endorsed preferences for flexible ways to identify and order PGx tests and multigene panel tests; opinions on whether test methodology should be included in the test name were divergent. The results could be used for both informing the VA's new electronic health records implementation (including how PGx tests are searched for and ordered) and for providing insights for other health systems implementing PGx-testing programs.
• Curry, S. C., Padilla-Jones, A., Ruha, A. M., O'Connor, A. D., Kang, A. M., Wilkins, D. G., Jaeschke, H., Wilhelms, K., Gerkin, R. D., & , A. A. (2019). The Relationship Between Circulating Acetaminophen-Protein Adduct Concentrations and Alanine Aminotransferase Activities in Patients With and Without Acetaminophen Overdose and Toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 15(3), 143-155.
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  Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose.
• Gallo, T., Curry, S. C., Padilla-Jones, A., Heise, C. W., Ramos, K. S., Woosley, R. L., & Raschke, R. A. (2019). A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk. Journal of thrombosis and haemostasis : JTH, 17(2), 383-388.
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  Essentials Current risk scores for heparin-induced thrombocytopenia (HIT) are not computer-friendly. We compared a new computerized risk score with the 4Ts score in a large healthcare system. The computerized risk score agrees with the 4Ts score 85% of the time. The new score could potentially improve HIT diagnosis via incorporation into decision support. SUMMARY: Background (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The 4Ts score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation. Objectives Our main objective was to develop an HIT computerized risk (HIT-CR) scoring system that provides platelet count surveillance for timing and degree of thrombocytopenia to identify those for whom diagnostic testing should be considered. Our secondary objective was to evaluate clinical management and subsequent outcomes in those identified as being at risk for HIT. Methods We retrospectively analyzed data from a stratified sample of 150 inpatients treated with heparin to compare the performance of the HIT-CR scoring system with that of a clinically calculated 4Ts score. We took a 4Ts score of ≥ 4 as the gold standard to determine whether HIT diagnostic testing should be performed. Results The best cutoff point of the HIT-CR score was a score of 3, which yielded 85% raw agreement with the 4Ts score and a kappa of 0.69 (95% confidence interval 0.57-0.81). Ninety per cent of patients with 4Ts score of ≥ 4 failed to undergo conventionally recommended diagnostic testing; 38% of these experienced persistent, unexplained thrombocytopenia, and 4% suffered life-threatening thrombotic complications suggestive of undiagnosed HIT. Conclusion The HIT-CR scoring system is practical for computerized CDS, agrees well with the 4Ts score, and should be prospectively evaluated for its ability to identify patients who should be tested for HIT.
• Heise, C. W., Agarwal, S., & Agarwal, S. (2019). Ocular Exposures Reported to Poison Control Centers From 2011 to 2015.. American journal of ophthalmology, 204, 46-50. doi:10.1016/j.ajo.2019.02.037
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  To identify and characterize the ocular exposures reported to poison control centers over a 5-year period from 2011 to 2015 in the United States..Pooled cross-sectional study..Callers to poison control centers..We retrospectively analyzed data from 477 274 calls for ocular exposure to the National Poison Data System. Major medical outcomes, reason for exposure, location of exposure, and causative xenobiotic were evaluated..A mean volume of 95 454 calls per year were reported to poison control centers, with most exposures occurring unintentionally, at home, and predominantly in children under 5 years of age. Most serious adult exposures occurred at work owing to alkali exposures. There was an increasing incidence in exposures in those over 64 years old. The most common treatment provided was irrigation and wash for the affected eye..Children under 5 are most susceptible; they may have permanent disability owing to laundry detergent exposure; and concerted intervention is needed in this age group. Many serious adult exposures occurred at work owing to alkali exposures.
• Romero, K., Woosley, D., Gallo, T., Tate, J., Heise, C., & Woosley, R. (2019). Drug labels, QT prolongation and ECG recommendations. Cardiology Today.
• Woosley, R. D., Romero, K., Heise, C. W., Gallo, T., Tate, J., & Woosley, R. L. (2019). Summary of Torsades de Pointes (TdP) Reports Associated with Intravenous Drug Formulations Containing the Preservative Chlorobutanol.. Drug safety, 42(7), 907-913. doi:10.1007/s40264-019-00804-7
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  Drug-induced torsades de pointes (TdP) is a potentially lethal ventricular arrhythmia that is associated with drugs that prolong the QT interval on the electrocardiogram (ECG) due to their interference with the cardiac potassium current, IKR. Intravenous (IV) formulations of methadone have been associated with TdP and contain the preservative chlorobutanol, which, like methadone, blocks IKR. The combinations of chlorobutanol with methadone or terfenadine, another IKR blocker, produce synergistic IKR block..The aim of this study was to examine and summarize the evidence available to address the question: what other IV drug formulations contain chlorobutanol and are they associated with TdP?.IV drug products containing the preservative chlorobutanol were identified by searching the websites DailyMed ( https://dailymed.nlm.nih.gov/dailymed/index.cfm ) and Drugs@FDA ( https://www.accessdata.fda.gov/scripts/cder/daf/ ). For each drug identified, PubMed and the FDA's Adverse Event Reporting System (FAERS) were searched for reports of TdP and/or QT prolongation and FAERS data were analyzed for disproportionality of reports..The search found nine drugs (methadone, epinephrine, papaverine, oxytocin, vasopressin, testosterone, estradiol, isoniazid, and desmopressin) that contain chlorobutanol 2.5 (n = 1) or 5.0 mg/mL. All nine drugs had reports of QT prolongation or TdP reported in FAERS and all but estradiol, testosterone, desmopressin, and isoniazid had reports of QT prolongation or TdP in PubMed. Two of the nine drugs (epinephrine and methadone) had positive signals (by disproportionality analysis) for TdP in FAERS (EB05 2.88 and 23.81, respectively) and four (methadone, epinephrine, papaverine, and vasopressin) were reported in published articles as the suspect drugs in cases of TdP..The pharmacologic profile of chlorobutanol (synergistic IKR block) and its association with reports of TdP and QT prolongation suggest the need for a full evaluation of its cardiac safety when used as a preservative in IV drug and vitamin formulations.
• Heise, C. W., Ruha, A., Padilla-jones, A., Gerkin, R. D., & Hayek, C. T. (2018). Clinical predictors of tissue necrosis following rattlesnake envenomation.. Clinical toxicology (Philadelphia, Pa.), 56(4), 281-284. doi:10.1080/15563650.2017.1371311
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  Rattlesnake envenomation (RSE) causes edema, hemotoxicity and tissue necrosis. Necrosis may result in permanent disability..To study patient-related factors associated with tissue necrosis after Crotalus envenomation..Prospective cohort study of patients admitted to the Medical Toxicology service with diagnosis of RSE between April 2011 and November 2014. Inclusion criteria were age ≥18 years and upper extremity (UE) envenomation site. Primary outcome was tissue necrosis, including dermonecrosis, manifesting as bullae. Secondary outcome was amputation..77 subjects, age 18 to 88 years, met inclusion criteria. Rattlesnake species was unknown in most cases. All received Fab antivenom. 62 (82%) had a digital envenomation. 31 (40.3%) had necrosis. Necrotic area ranged from 0.1 cm2 to 14 cm2. Procedural interventions, (superficial debridement, dermotomy, surgical exploration, and operative debridement of devitalized tissue) occurred in 25 (32.5%). Five (6.5%) underwent dermotomy and 6 (7.8%) operative debridement. No amputations were performed. Patients with cyanosis on presentation had increased risk of developing necrosis (11/12; RR 2.98 95% CI 1.99-4.46). Ecchymosis on presentation was also associated with increased risk of necrosis (24/32; RR 4.04 95% CI 2.08-7.86). Patients with social or regular ethanol use were more likely to develop necrosis than those without (28/53; RR 4.23 95% CI 1.42-12.6). Regular cocaine use was associated with increased risk of operative debridement (4/6; RR 9.13 95% CI 2.33-35.8). A nonsignificant risk of operative debridement occurred with tobacco use (RR 1.14 95%CI 0.99-1.31 p = 0.09). Time to antivenom did not correlate with risk of necrosis..UE RSE patients who presented with cyanosis, ecchymosis or history of ethanol use were at increased risk of developing necrosis. Cocaine use was associated with increased risk of operative debridement.
• Woosley, R. L., Black, K., Heise, C. W., & Romero, K. (2018). CredibleMeds.org: What does it offer?. Trends in cardiovascular medicine, 28(2), 94-99.
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  Since the 1990s, when numerous non-cardiac drugs were first recognized to have the potential to prolong the QT interval and cause torsades de pointes (TdP), clinicians, drug regulators, drug developers, and clinical investigators have become aware of the complexities of assessing evidence and determining TdP causality for the many drugs being marketed or under development. To facilitate better understanding, the Arizona Center for Education and Research on Therapeutics, known as AZCERT, has developed the CredibleMeds.org website which includes QTdrugs, a listing of over 220 drugs placed in four risk categories based on their association with QT prolongation and TdP. Since the site was launched in 1999, it has become the single and most reliable source of information of its kind for patients, healthcare providers, and research scientists. Over 96,000 registered users rely on the QTdrugs database as their primary resource to inform their medication use, their prescribing or their clinical research into the impact of QT-prolonging drugs and drug-induced arrhythmias. The QTdrugs lists are increasingly used as the basis for clinical decision support systems in healthcare and for metrics of prescribing quality by healthcare insurers. A free smartphone app and an application program interface enable rapid and mobile access to the lists. Also, the CredibleMeds website offers numerous educational resources for patients, educators and healthcare providers that foster the safe use of medications.
• Heise, C. W., & Brooks, D. E. (2017). Ayahuasca Exposure: Descriptive Analysis of Calls to US Poison Control Centers from 2005 to 2015. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 13(3), 245-248.
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  Ayahuasca is a hallucinogenic plant preparation which usually contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea originates from the Amazon Basin where it is used in religious ceremonies. Because interest in these religious groups spreading as well as awareness of use of ayahuasca for therapeutic and recreational purposes, its use is increasing. Banisteriopsis caapi is rich in β-carbolines, especially harmine, tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI) activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include hallucination, dissociation, mood alteration and perception change. Undesired findings previously reported are nausea, vomiting, hypertension, and tachycardia.
• Heise, C. W., Malashock, H., & Brooks, D. E. (2017). A review of vilazodone exposures with focus on serotonin syndrome effects. Clinical toxicology (Philadelphia, Pa.), 55(9), 1004-1007.
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  Vilazodone is an antidepressant with selective serotonin reuptake inhibition and partial 5HT1A agonism. Serotonin syndrome is believed to be due to excessive stimulation of 5-HT2A and 5-HT1A receptors, resulting in the clinical triad of altered mentation, autonomic instability and neuromuscular abnormalities. The goal of this study is to define serotonergic effects after vilazodone exposure.
• Heise, C. W., Ruha, A. M., Padilla-Jones, A., Truitt Hayek, C., & Gerkin, R. D. (2017). Clinical predictors of tissue necrosis following rattlesnake envenomation. Clinical toxicology (Philadelphia, Pa.), 1-4.
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  Rattlesnake envenomation (RSE) causes edema, hemotoxicity and tissue necrosis. Necrosis may result in permanent disability.
• Woosley, R. L., Romero, K., Heise, C. W., Gallo, T., Tate, J., Woosley, R. D., & Ward, S. (2017). Adverse Drug Event Causality Analysis (ADECA): A Process for Evaluating Evidence and Assigning Drugs to Risk Categories for Sudden Death. Drug safety, 40(6), 465-474.
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  Growing evidence indicates that many drugs have the ability to cause a potentially lethal cardiac arrhythmia, torsades de pointes (TdP). This necessitates the development of a compilation of drugs that have this potential toxicity. Such a list is helpful in identifying the etiology of TdP in patients taking multiple drugs and assists decision making by those caring for patients at high risk of TdP. The Arizona Center for Education and Research on Therapeutics (AZCERT) has developed a process to standardize the identification of drugs and place them in risk categories for their clinical ability to cause TdP and QT prolongation. AZCERT's Adverse Drug Event Causality Analysis (ADECA) utilizes 16 types of data drawn from four sources to compile an open-source knowledge base, QTdrugs, which is maintained on the CredibleMeds.org website. Because the evidence for most drugs is incomplete, the ADECA process is used to place drugs into one of three categories that represent different levels of certainty: known TdP risk, possible TdP risk, and conditional TdP risk. Each category has strict evidentiary requirements for clinical evidence of TdP and/or QT prolongation. These are described in this paper. Because evidence can evolve over time, the ADECA process includes the continuous gathering and analysis of newly emerging evidence to revise the lists. The QTdrugs lists have proven to be a valued, readily available, commercial influence-free resource for healthcare providers, patients, researchers, and authors of consensus guidelines for the safe use of medicines.
• Heise, C. W., Skolnik, A. B., Raschke, R. A., Owen-Reece, H., & Graeme, K. A. (2016). Two Cases of Refractory Cardiogenic Shock Secondary to Bupropion Successfully Treated with Veno-Arterial Extracorporeal Membrane Oxygenation. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 12(3), 301-4.
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  Bupropion inhibits the uptake of dopamine and norepinephrine. Clinical effects in overdose include seizure, status epilepticus, tachycardia, arrhythmias, and cardiogenic shock. We report two cases of severe bupropion toxicity resulting in refractory cardiogenic shock, cardiac arrest, and repeated seizures treated successfully. Patients with cardiovascular failure related to poisoning may particularly benefit from extracorporeal membrane oxygenation (ECMO). These are the first cases of bupropion toxicity treated with veno-arterial EMCO (VA-ECMO) in which bupropion toxicity is supported by confirmatory testing. Both cases demonstrate the effectiveness of VA-ECMO in poisoned patients with severe cardiogenic shock or cardiopulmonary failure.
• Heise, C. W., Beutler, D., Bosak, A., Orme, G., Loli, A., & Graeme, K. (2015). Massive Atenolol, Lisinopril, and Chlorthalidone Overdose Treated with Endoscopic Decontamination, Hemodialysis, Impella Percutaneous Left Ventricular Assist Device, and ECMO. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(1), 110-4.
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  Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome.
• Lovecchio, F., & Heise, C. W. (2015). Accidental pediatric ingestions of medical marijuana: a 4-year poison center experience. The American journal of emergency medicine, 33(6), 844-5.

Poster Presentations

• Mark, Z., Nguyen, M., Rivas, S., Heise, C., Maghari, S., & Gallo, T. (2023, June). Medications with actionable safety and efficacy pharmacogenomic recommendations in Veteran patients. PGRN 2023 Annual Scientific Meeting. Memphis, TN.
• Gallo, T., Heise, C., & Curry, S. (2019, Nov). Identifying target populations for pharmacogenomic testing implementation using a benefit tool. Re-imagine Health: Is my fate in my genes. Phoenix, AZ.