OBJECTIVE:Although palpitations are common in midlife women and may have long-term effects on cardiovascular health and longevity, little is known about underlying electrocardiogram findings, real-time palpitations reporting, or correlates. This hypothesis-generating pilot study compared midlife perimenopausal and postmenopausal women with and without palpitations on electrocardiogram findings, real-time palpitations reporting, and potential correlates. METHODS:In this prospective, longitudinal, descriptive, comparative pilot study, 15 midlife women with and 15 without palpitations provided data. They wore an ambulatory electrocardiogram patch for 14-28 days, prospectively recorded palpitations via event button presses and daily diaries, recorded vasomotor symptoms in daily diaries, provided blood samples, and completed questionnaires. RESULTS:There were no group differences in age [Md (IQR) = 56 (50, 59) vs. 55 (53, 57) with an age range of 46 to 62 in both groups] or menopausal status. The palpitations group had significantly lower heart rate variability and longer runs of atrial tachycardia. Button press data indicated that 50% of the palpitations group experienced palpitations (1) one third or more of all nights on the study, (2) nearly half of all days on the study, or (3) once or more per 24 hours on the study. Symptoms occurred during altered rhythms and normal sinus rhythm, though the latter seemed more common at night. Palpitations reporting was not related to demographics, clinical variables, biomarkers, anxiety, or somatosensory awareness but was related to having vasomotor symptoms and diabetes. CONCLUSION:The pilot study findings revealed some important hypothesis-generating differences that are worthy of further investigation in a larger study.

ABSTRACT:Testosterone and dihydrotestosterone (DHT) attenuate drug-induced lengthening of ventricular repolarization, but it is unknown whether they influence drug-induced torsades de pointes (TdP). We tested the hypothesis that DHT reduces the incidence and severity of drug-induced TdP. Male New Zealand white rabbits underwent orchiectomy and were implanted with 2 subcutaneous sustained-release pellets containing DHT 50 mg (100 mg, n = 23) or placebo (n = 20). After 7 days, hearts were excised, mounted, and perfused with modified Krebs-Henseleit solution. The atrioventricular node was destroyed manually. Dofetilide 100 nM was perfused for 30 minutes. Median (Q 1 , Q 3 ) serum DHT concentrations were higher in DHT-treated rabbits [314.0 (232.5, 388.6) vs. 32.5 (28.5, 36.2) ng/dL, P < 0.0001]. The incidence of TdP in the DHT and placebo groups was 6/23 (26%) versus 8/20 (40%), respectively ( P = 0.33). In hearts that developed TdP, the median (Q 1 , Q3) number of episodes was lower in the DHT group [2 (2, 3.5) vs. 18.5 (12.5, 20.5), P = 0.01]. The median time to first TdP episode was longer [18.5 (17.3, 21.3) vs. 10.5 (12.5, 20.5) minutes, P = 0.01], and the TdP burden (median total number of TdP beats per heart) was lower in the DHT group [11.5 (9.5-46.5) vs. 271 (99.3-440.3) beats, P = 0.007]. Pre-dofetilide Fridericia-corrected QT intervals were shorter in the DHT group [377 (366, 390) vs. 385 (378, 401) ms, P = 0.02]. Maximum Fridericia-corrected QT interval during dofetilide perfusion was shorter in the DHT group [399 (390, 410) vs. 414 (399, 442) ms, P = 0.007]. In conclusion, DHT diminishes the severity of dofetilide-induced TdP.

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.

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.

Background: An appointment -based medication synchronization (ABMS) is a service whuch aligns patients' chronic medications to a predetermined routine pickup date and includes a comprehensive medication review or other clinical appointment at the pharmacy. Objective(s): We compared healthcare utilization outcomes (outpatient, inpatient, emergency department visits, and pharmacy utilization) of Medicare beneficiaries enrolled in a med-sync program to beneficiaries not enrolled in such a program. Methods: This retrospective cohort study included Medicare beneficiaries obtaining medications from pharmacies providing ABMS. All Medicare inpatient, outpatient, emergency, and pharmacy claims data from 2014 to 2016 obtained from the Research Data Assistance Center. These pharmacy claims were used to create med-sync (n = 13,193) and non-med-sync cohorts (n = 156,987). All patients were followed longitudinally for 12 months before and after a 2015 index or enrollment date. Baseline characteristics were used to create a logistic regression model for propensity score matching. A 1:1 greedy nearest neighbor matching algorithm was adapted for sequentially matching both cohorts. Difference in differences (DID) was used to compare mean changes in health care utilization outcomes (outpatient, inpatient, ED visits, and pharmacy utilization) between cohorts. Results: After matching, 13,193 beneficiaries in each cohort were used for analysis. DIDs for mean of health care utilizations were statistically significantly lower in the med-sync cohort than the non-med-sync cohort for outpatient visits (DID 0.012, P = 0.0073) and pharmacy utilization (DID 0.013, P < 0.0001). There was not a statistically significant DID for inpatient and ED visits between cohorts. Conclusion: Outpatient and pharmacy utilization changes were statistically significantly lower in the med-sync cohort than the non-med-sync cohort in the 12 months after enrollment. Lower pharmacy utilization could be caused by reducing duplicate prescriptions during synchronized refills or optimization of therapy during medication reviews if patients are enrolled in appointment -based model med-sync. (c) 2024 Published by Elsevier Inc. on behalf of the American Pharmacists Association.

Background Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk. Methods We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. Twelve‑lead electrocardiograms were obtained prior to ibutilide and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak (J-Tpeakc), representing early repolarization, were measured by an investigator blinded to study groups. Results Baseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ± 10 vs 73 ± 8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was greater in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.003]. The area under the effect curve from 0 to 8 hours following ibutilide (including the 10-minute infusion) (AUEC0-8.17) for Tpeak-Tend was also larger in the HFpEF group (600 ± 42 vs. 543 ± 49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC0-8.17 for J-Tpeakc in the two groups were not significantly different. Conclusion HFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization.

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.

Background: Medication synchronization (med-sync) aligns patients' monthly or quarterly chronic medications to a predetermined single pickup date at a community pharmacy. The study objective was to examine med-sync enrollment disparities based on Medicare beneficiaries' predisposing, enabling, and need characteristics. Methods: This was a retrospective cohort study using a Medicare dataset of beneficiaries receiving medications from pharmacies that self-identified as providing med-sync. Medicare beneficiaries who were continuously enrolled in fee-for-service medical and pharmacy benefits during the study period (2014-2016) were included. Study cohorts (med-sync and non-med-sync patients) were defined, and bivariate and multivariable logistic regression analyses were performed. Andersen's Health Services Utilization Model guided our inclusion of predisposing, enabling, and need characteristics to examine for association with med-sync enrollment. Results: A total of 170,180 beneficiaries were included, of which 13,193 comprised the medsync cohort and 156,987 comprised the non-med-sync cohort. Bivariate logistic regression analysis revealed statistically significant differences (P < 0.05) in cohorts based on age, geographic region, type of residence, number of unique chronic medications, comorbidities, outpatient visits, and inpatient hospitalizations. Beneficiaries had higher odds of being enrolled in med-sync with increasing age (adjusted odds ratio [AOR] 1.003 [95% CI 1.001 -1.0 05]) and if they resided in the Northeast (AOR 1.094 [95% CI 1.018-1.175]), South (AOR 1.109 [95% CI 1.035-1.188]), and West (AOR 1.113 [95% CI 1.020-1.215]) than those in the Midwest. Beneficiaries residing in nonmetro areas had lower odds of enrollment (AOR 0.914 [95% CI 0.863-0.969]) than those in metro areas. Beneficiaries with previous fewer inpatient hospitalizations (AOR 0.945 [95% CI 0.914-0.977]) were more likely to be enrolled, and those with more outpatient visits (AOR 1.003 [95% CI 1.001-1.004]) were more likely to be enrolled. Those taking a higher number of oral chronic medications (AOR 1.005 [95% CI 1.002-1.0 08]) had greater odds of enrollment in med-sync.Conclusions: Med-sync program expansion opportunities exist to address potential enrollment disparities based on age, geographic region, metropolitan area, and prior health utilization. Further studies are needed to develop and examine strategies among pharmacies to improve med-sync enrollment outreach to these subgroups of patients. (c) 2022 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Medication non-adherence is a significant public health problem. Patient-reported outcomes (PROs) offer a rich data source to facilitate resolution of medication non-adherence. PatientToc™ is an electronic PRO data collection software originally implemented at primary care practices in California, United States (US). Currently, the use of standardized PRO data collection systems in US community pharmacies is limited. Thus, we are conducting a two-phase evaluation of the spread and scale of PatientToc™ to US Midwestern community pharmacies. This report focuses on the first phase of the evaluation. The objective of this phase was to prepare for implementation of PatientToc™ in community pharmacies by conducting a pre-implementation developmental formative evaluation to (1) identify potential barriers, facilitators, and actionable recommendations to PatientToc™ implementation and (2) create a draft implementation toolkit. Data collection consisted of demographics, observations, audio-recorded contextual inquiries, and semi-structured interviews with staff (e.g., primary care providers, pharmacists, pharmacy technicians) and patients during 1-day site visits to a purposive sample of (1) primary care practices currently using PatientToc™ and (2) community pharmacies in Indiana, Wisconsin, and Minnesota interested in the future use of PatientToc™. Post-visit site observation debriefs were also audio-recorded. Verbatim transcripts of all recordings were coded using deductive/inductive approaches and intra-/inter-site summaries were produced identifying potential barriers, facilitators, and actionable recommendations mapped to the Consolidated Framework for Implementation Research constructs. A stakeholder advisory panel engaged in an Evidence-Based Quality Improvement (EBQI) implementation process. This included “member checking” and prioritizing findings, and feedback on the adapted PatientToc™ application, implementation strategies, and accompanying toolkit for community pharmacy implementation. Two primary care practices, nine pharmacies, and 89 individuals participated. Eight major themes (four barriers and four facilitators) and 14 recommendations were identified. Throughout the four EBQI sessions, the panel (1) confirmed findings; (2) designated high priority recommendations: (a) explain PatientToc™ and its benefits clearly and simply to patients, (b) ensure patients can complete questionnaires within 10 min, and (c) provide hands-on training/resources for pharmacy teams; and (3) provided feedback on the adapted PatientToc™ application and finalized toolkit items for initial community pharmacy implementation. Adoption of electronically captured PROs in community pharmacies is warranted. The implementation strategies systematically developed in this study can serve as a model for implementation of technology-driven health information patient care services, in the understudied context of community pharmacies.

Introduction: Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced proarrhythmia. It is unknown whether patients with HF with preserved ejection fraction (HFpEF) are also at increased risk. Hypothesis: The risk of drug-associated ventricular tachycardia (VT) and sudden cardiac arrest (SCA) is increased in patients with HFpEF. Methods: Using Medicare enrollment in fee-for-service medical and pharmacy benefits (2014 to 2016) and ICD-9/10 codes, we identified patients taking drugs known to cause torsades de pointes (TdP drugs; www.crediblemeds.org) and non-TdP drug users among three groups: HFrEF (n=31,422), HFpEF (n=40,012), and no HF (n=633,558). Multinomial propensity score-matching was performed to minimize baseline differences in covariates (patient demographics, comorbidities, health care utilization and drug history). Cochran-Mantel-Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate hazard ratios (HRs) and test the association of VT and SCA among TdP drug users with HFpEF, HFrEF, and no HF. Results: Of 23,910 TdP drug users with HFrEF, VT and SCA occurred in 4,263 (17.8%) and 493 (2.1%) patients, respectively. In comparison, among 31,359 TdP drug users with HFpEF, VT and SCA occurred in 1,570 (5.0%) and 340 (1.1%) patients. VT and SCA occurred in 3,154 (0.8%) and 528 (0.1%) of 384,824 TdP drug users without HF. The overall risk of both VT and SCA was increased in patients with HFrEF and in those with HFpEF (Table). The risk of VT associated with TdP drugs was increased across the overall population. Use of TdP drugs significantly increased the risk of VT and SCA in patients with HFrEF, but not in patients with HFpEF. Conclusions: The risk of VT and SCA associated with drugs known to cause TdP was increased in patients with HFrEF but not in those with HFpEF.

Introduction: 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) also increases the risk. Dofetilide (D) and sotalol (S) are potent QT interval-prolonging agents that are commonly used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. Hypothesis: The risk of QTc prolongation associated with D or S (D/S) is increased in patients with HFpEF. Methods: The data source was electronic health records from the Indiana Network for Patient Care (February 2010 to May 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, absence of QT interval records, and no validated record of using D/S, we identified patients taking D/S among three groups: HFrEF (n=138), HFpEF (n=109), and no HF (n=729). Cochran-Mantel-Haenszel statistics were used to compare baseline characteristics. QT interval prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during D/S therapy. Unadjusted odds ratios (OR) of QT interval prolongation were determined by univariate analysis, and 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. Results: QTc prolongation associated with D/S occurred in 51.2% of patients with HFpEF, 70.1% of patients with HFrEF, and 29.4% of patients with no HF. 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, as well as in those with HFrEF, compared to those with no evidence of HF (Table). Conclusions: The odds of QT interval prolongation among inpatients receiving D/S were increased in patients with HFpEF and HFrEF compared to those who did not have HF.

Medication synchronization (med-sync) aligns patients’ chronic medications to a predetermined routine pickup date at a community pharmacy. An appointment-based model (ABM) med-sync service includes a comprehensive medication review or other clinical appointment at the pharmacy. We compared the cost and healthcare utilization outcomes of Medicare beneficiaries enrolled in an ABM med-sync program to beneficiaries not enrolled in such a program.