Electrocardiography

Objective: To assess the effective dose range, safety, and tolerability of the novel selective orexin-2 receptor antagonist seltorexant in insomnia disorder.

Design, setting, and participants: This randomized, double-blind, active- and placebo-controlled, dose-finding, polysomnography study was conducted from November 2017 to April 2019 at 55 sites in 6 countries and analyzed in August 2019. The timeline for submission of this data for publication was impacted by internal strategic decision-making. Adults (aged 18-64 years) and older adults (aged 65-85 years) with insomnia (Insomnia Severity Index score ≥15) and no psychiatric comorbidity were included.

Interventions: Participants were randomized 1:1:1:1:1 to receive nightly oral-seltorexant (5 mg, 10 mg, or 20 mg), placebo, or zolpidem (5-10 mg) for 14 days.

Main outcomes and measures: Primary and key secondary outcomes included the dose-response relationship of night 1 latency to persistent sleep (LPS) and wake after sleep onset over the first 6 hours (WASO-6). Other secondary outcomes included night 13 LPS and WASO-6. Due to asymmetrical distributions of LPS and WASO-6 at baseline, log transformation was applied and results were expressed as back-transformed least-squares mean (LSM) ratios for comparisons between groups.

Results: Overall, 364 participants (mean [SD] age, 57.8 [12.4] years; 246 [67.6%] female) received seltorexant, 5 mg (n = 71), 10 mg (n = 74), or 20 mg (n = 71); placebo (n = 75); or zolpidem (n = 73). The night 1 dose-response relationship for LPS was significant (with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models), with greater improvements in seltorexant, 10 mg and 20 mg, vs placebo (10 mg: LSM ratio, 0.64; 90% CI, 0.51-0.81; 20 mg: LSM ratio, 0.51; 90% CI, 0.41-0.64) and in seltorexant, 20 mg, vs zolpidem (LSM ratio, 0.71; 90% CI, 0.57-0.88). The night 1 dose-response relationship for WASO-6 was also significant, with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models (seltorexant, 10 mg: LSM ratio, 0.68; 90% CI, 0.55-0.85; seltorexant, 20 mg: LSM ratio, 0.60; 90% CI, 0.48-0.74). Night 1 LPS and WASO-6 improvements were maintained on night 13 for seltorexant, 10 mg and 20 mg, but diminished for zolpidem. On night 13, compared with zolpidem, seltorexant, 10 mg and 20 mg, improved LPS by 30% and 28%, respectively, and seltorexant, 20 mg, improved WASO-6 by 31%. Treatment-emergent adverse events (TEAEs) were lower across the combined seltorexant doses (73/216 [33.8%]) relative to placebo (37/75 [49.3%]) and zolpidem (31/73 [42.5%]). Two participants experienced serious TEAEs during the double-blind phase (1 in the seltorexant, 20 mg, group and 1 in the zolpidem group). Three participants in the seltorexant, 5 mg, and 1 in the seltorexant, 20 mg, group experienced asymptomatic electrocardiogram-related TEAEs leading to discontinuation.

Conclusions and relevance: Among participants with insomnia in this study, seltorexant, 10 mg and 20 mg, improved sleep initiation and maintenance throughout 14 days of treatment. Seltorexant was generally well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT03375203.

Author/s:

Sofie Mesens, Andrew D Krystal, Rama Melkote, Haiyan Xu, Gahan Pandina, Jay B Saoud, Remy Luthringer, Adam Savitz, Wayne C Drevets

Tilt Table Testing

Alex Haga — Tue, 23 Apr 2024 17:41:24 +0000

Date Added:

April 23, 2024

Journal/Publication:

JAMA

Publisher:

JAMA

Publication Date:

April 11, 2024

URL:

Tilt Table Testing

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.0004

Keywords

Cardiac Catheterization

PMID (1):

38602671

MeSH

hydrocortisone

Methacholine Chloride

Cardiac Catheterization

A summary and example of how to use tilt table testing in patients with syncope and various other fairly common symptoms. James W. Mold, MD, MPH

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A 43-year-old woman presented with a 1-year history of recurring symptoms of sudden onset of fatigue, palpitations, dyspnea, chest pain, lightheadedness, and nausea that were associated with standing and resolved with sitting. These symptoms began 1 month after mild COVID-19 infection. At presentation, while supine, blood pressure (BP) was 123/70 mm Hg and heart rate (HR) was 90/min; while seated, BP was 120/80 and HR was 93/min; after standing for 1 minute, BP was 124/80 and HR was 119/min. Physical examination results were normal. Oxygen saturation was 98% at rest while breathing room air. She had no oxygen desaturation during a 6-minute walk test but walked only 282 m (45% predicted). Complete blood cell count, morning cortisol, and thyrotropin blood levels were normal. Electrocardiogram (ECG), chest computed tomography, pulmonary function testing, methacholine challenge, bronchoscopy, echocardiography, and cardiac catheterization findings were normal. During tilt table testing, the patient experienced lightheadedness and nausea when moved from horizontal to the upright position. Results of the tilt table test are shown in the Table and Figure.

Author/s:

Chesire, W.P., Dudenkov, D.V., Munipalli, B.

Tilt Table Testing

Alex Haga — Tue, 23 Apr 2024 17:40:59 +0000

Date Added:

April 23, 2024

Journal/Publication:

JAMA

Publisher:

JAMA

Publication Date:

April 11, 2024

URL:

Tilt Table Testing

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.0004

Keywords

Cardiac Catheterization

PMID (1):

38602671

MeSH

hydrocortisone

Methacholine Chloride

Cardiac Catheterization

A summary and example of how to use tilt table testing in patients with syncope and various other fairly common symptoms. James W. Mold, MD, MPH

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Author/s:

Chesire, W.P., Dudenkov, D.V., Munipalli, B.

Diagnosing acute aortic syndrome: a Canadian clinical practice guideline

Brian Desmarais — Mon, 20 Jul 2020 16:29:20 +0000

Date Added:

July 20, 2020

Journal/Publication:

Canadian Medical Association Journal

Publication Date:

July 20, 2020

Issue:

Volume:

192

Pages:

E832-E843

URL:

Diagnosing acute aortic syndrome: a Canadian clinical practice guideline

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1503/cmaj.200021

MeSH

risk factors

fibrin fragment D

Fibrin Fibrinogen Degradation Products

tomography, x-ray computed

A guideline from Canada on diagnosis of acute aortic syndrome (dissection, thrombosis, or perforating ulceration of the aorta). James W. Mold, MD, MPH

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Not available.

Author/s:

Ohle, R., Yan, J.W., Yadav, K., Cournoyer, A., Savage, D.W., Jetty, P., Atoui, R., Bittira, B., Wilson, B., Gupta, A., Coffey, A., Callaway, Y., Middaugh, J., Ansell, D., Rubens, F., Bignucolo, S.J., Scott, T., McIsaac, S., Lang, E.

Impact of High Volume Energy Drink Consumption on Electrocardiographic and Blood Pressure Parameters: A Randomized Trial

Brian Desmarais — Wed, 05 Jun 2019 00:44:50 +0000

Date Added:

June 4, 2019

Journal/Publication:

Journal of the American Heart Association

Publisher:

The American Heart Association

Publication Date:

June 4, 2019

URL:

Impact of High Volume Energy Drink Consumption on Electrocardiographic and Blood Pressure Parameters: A Randomized Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

https://doi.org/10.1161/JAHA.118.011318

Keywords

MeSH

Blood Pressure Determination

As we all suspected, energy drinks aren’t good for you. They increase BP and prolong the EKG QTc interval.

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Abstract

Background

Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers.

Methods and Results

A randomized, double‐masked, placebo‐controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6‐day washout period in between. The primary end point of QTc interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central blood pressures were measured at baseline, and every 30 minutes for 240 minutes. A repeated‐measures 2‐way analysis of variance was performed with the main effects of intervention, time, and an interaction of intervention and time. Thirty‐four participants were included (age 22.1±3.0 years). The interaction term of intervention and time was statistically significant for Bazett's corrected QT interval, Fridericia's corrected QT interval, QT, PR, QRS duration, heart rate, systolic blood pressure, diastolic blood pressure, central systolic blood pressure, and central diastolic blood pressure (all P<0.001). The maximum change from baseline in Bazett's corrected QT interval for drinks A, B, and placebo were +17.9±13.9, +19.6±15.8, and +11.9±11.1 ms, respectively (P=0.005 for ANOVA) (P=0.04 and <0.01, respectively compared with placebo). Peripheral and central systolic and diastolic blood pressure were statistically significantly different compared with placebo (all P<0.001).

Conclusion

Energy drinks significantly prolong the QTc interval and raise blood pressure.

Author/s:

Kaul, Sanjay, Shah, S.A., Szeto, A.H., Farewell, Raechel, Shek, Allen, Fan, Dorothy, Quach, K.N., Bhattacharyya, Mouchumi, Elmiari, Jasmine, Chan, Winny, O'Dell, Kate, Nguyen, Nancy, McGaughey, T.J., Nasir, J.M.