Trial Outcomes & Findings for Impact of Beta-blockers on Physical Function in HFpEF (NCT NCT04767061)

Last Updated: 2023-09-08

Results Overview

The wearable activity monitoring device measures daily step count. Due to the nature of N-of-1 trials, the duration of a subject's periods varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 and 6 weeks. We will compare average step counts over 2-week periods, which will be the final 2 weeks of each period when subjects are either on their "home" (ON Beta Blockers) or minimally tolerated (OFF Beta Blockers) dose. The outcome measure data is the mean collected during the outcome measure time frame.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

9 participants

Primary outcome timeframe

The maximum amount of time a subject could have been assessed for this outcome measure is 8-weeks (last 2 weeks of each period for up to 4 periods).

Results posted on

2023-09-08

Participant Flow

Participant milestones

Participant milestones
Measure	Beta Blocker ABAB Sequence This arm will follow an ABAB sequence. "A" representing ON beta blockers and "B" representing OFF beta blockers. Subjects in this arm will continue their home dose during the initial A period, they will then crossover into Period 2, where dose reduction will begin until they are off of beta blockers. During Period 3, they will restart beta-blockers, gradually uptitrating until reaching their home dose and finally during period 4, we will again conduct a dose reduction until off of beta blockers. Beta blockers: The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with 4 periods, each period lasting up to 6 weeks. During the On period (A), subjects will be on their beta blocker. During the Off period (B), their beta blockers will be down titrated and subsequently discontinued. Subjects will be randomized into either ABAB or BABA sequences.	Beta Blocker BABA Sequence This arm will follow a BABA sequence. "A" representing ON beta blockers and "B" representing OFF of beta blockers. Subjects in this arm will have their previously prescribed beta blocker dose reduced until they are completely off of beta blockers during Period 1. They will then crossover into Period 2, where uptitration will begin until they are back on their previously prescribed dose of beta blockers. During Period 3, we will again conduct a dose reduction, until the subject is off of beta blockers and finally during Period 4, we will uptitrate them back to their home dose of beta blockers. Beta blockers: The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with 4 periods, each period lasting up to 6 weeks. During the On period (A), subjects will be on their beta blocker. During the Off period (B), their beta blockers will be down titrated and subsequently discontinued. Subjects will be randomized into either ABAB or BABA sequences.
On or Off Beta Blockers Up to 6 Wks STARTED	5	4
On or Off Beta Blockers Up to 6 Wks COMPLETED	5	4
On or Off Beta Blockers Up to 6 Wks NOT COMPLETED	0	0
Down-titration/Up-titration Up to 6 Wks STARTED	5	4
Down-titration/Up-titration Up to 6 Wks COMPLETED	5	4
Down-titration/Up-titration Up to 6 Wks NOT COMPLETED	0	0
Up-titration/Down-titration Up to 6 Wks STARTED	0	2
Up-titration/Down-titration Up to 6 Wks COMPLETED	0	2
Up-titration/Down-titration Up to 6 Wks NOT COMPLETED	0	0
Down-titration/Up-Titration Up to 6 Wks STARTED	0	0
Down-titration/Up-Titration Up to 6 Wks COMPLETED	0	0
Down-titration/Up-Titration Up to 6 Wks NOT COMPLETED	0	0
Follow-up STARTED	5	4
Follow-up COMPLETED	5	4
Follow-up NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Impact of Beta-blockers on Physical Function in HFpEF

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 8-weeks (last 2 weeks of each period for up to 4 periods).

Population: One subject did not have any measurements from their activity monitoring device.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=8 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=8 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Physical Activity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Step Count on Wearable Activity Monitoring Device	2790.5 Count of Steps Standard Deviation 1,999.32	3167.3 Count of Steps Standard Deviation 1,901.65

PRIMARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Population: This population excludes subjects who did not complete the SPPB at both ON and OFF arms.

The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using the upper extremities, and balance while standing without a cane or walker. The balance test portion of the SPPB assesses the subject's ability to stand unassisted without the use of a cane or walker. Balance test scores range from 0 - 4 with higher scores indicating better ability to stand unassisted. Our research team conducted the balance test according to SPPB standards. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=7 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=7 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Balance Portion of a Modified Version of the Short Physical Performance Battery.	3.9 score on a scale Standard Deviation 0.38	3.6 score on a scale Standard Deviation 0.79

PRIMARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Population: This population excludes subjects who did not complete the SPPB at both ON and OFF arms.

The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using the upper extremities, and balance while standing without a cane or walker. The gait speed portion of the SPPB assesses the subject's lower extremity function. When comparing the number of seconds it takes to complete the 4-meter gait speed test, quicker speeds indicate better lower extremity function. Our research team conducted the 4-meter gait speed test according to SPPB standards, but have chosen on comparing the speed at which subjects were able to complete the test. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=7 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=7 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Gait Speed Portion of a Modified Version of the Short Physical Performance Battery.	4.3 seconds Standard Deviation 0.86	4.6 seconds Standard Deviation 1.0

PRIMARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Population: This population excludes subjects who did not complete the SPPB at both ON and OFF arms.

The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using the upper extremities, and balance while standing without a cane or walker. The chair rise portion of the SPPB assesses core strength. When comparing the number of seconds it takes to complete 5 chair rises, quicker speeds indicate better core strength. Our research team has chosen on comparing the speed at which subjects were able to complete the test. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the outcome measure time frame.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=7 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=7 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Chair Rise Portion of a Modified Version of the Short Physical Performance Battery.	16 seconds Standard Deviation 4.92	15.1 seconds Standard Deviation 5.08

PRIMARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 6-weeks. This outcome was measured at the end of the first and second visit.

Cardiopulmonary exercise testing (CPET) measures breath-by-breath oxygen production during symptom-limited exercise on a stationary bike. This permits the calculation of peak oxygen consumption (VO2). Percent predicted peak VO2 for body weight will also be calculated. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=9 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=9 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Exercise Capacity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Peak Oxygen Consumption (VO2) During Cardiopulmonary Exercise Test (CPET)	10.0 ml/kg/min Standard Deviation 2.7	11.4 ml/kg/min Standard Deviation 2.03

SECONDARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, weekly, end of period and intervention visits, and during follow-up.

The PROMIS-29 assesses 7 domains with 4 questions with an additional pain intensity numeric rating scale. The patients' answers to the PROMIS-29 are scored from 1-5 (except for the pain numeric rating scale). The sum of the PROMIS-29 is the raw score transformed into a final T-score metric. Scores are mapped so that the values follow a normal distribution with a population mean T-score of 50 and an SD of 10. Instead of having a min or max, the PROMIS-29 raw scores have been transformed into t-scores for comparison to a reference population (the US general population) with a mean of 50 and SD of 10. Scores lower than 50 indicate worse health compared to the US general population. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker before enrollment, therefore, each subject's respective period for the OFF and ON periods could range between 3 - 6 weeks. The values measured over the time points were averaged.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=9 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=9 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Patient-reported Quality of Life When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-29 (PROMIS-29) Physical Health Component	39.8 score on a scale Standard Deviation 6.60	40.0 score on a scale Standard Deviation 8.86
Change in Patient-reported Quality of Life When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-29 (PROMIS-29) Mental Health Component	46.8 score on a scale Standard Deviation 10.38	47.9 score on a scale Standard Deviation 7.50

SECONDARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, end of period and intervention visits, and during follow-up.

Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function) measures self-reported sexual function and satisfaction. Questions are ranked on a 6-point Likert scale, with higher scores indicating poorer sexual function and satisfaction. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame. The score ranges from 0-10 with higher scores meaning worsened sexual function.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=9 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=9 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Patient-reported Sexual Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function)	1.8 score on a scale Standard Deviation 1.97	2.1 score on a scale Standard Deviation 1.27

SECONDARY outcome

Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a) is a survey of patient-perceived cognitive deficits. Questions are ranked on a 5-point Likert scale, with higher scores indicating better cognitive function. Scores are mapped so the values follow a normal distribution with a population mean T-score of 50 and an SD of 10. Instead of having a min or max, the raw scores have been transformed into t-scores for comparison to a reference population (the US general population) with a mean of 50 and SD of 10. Scores lower than 50 indicate worse cognitive function compared to the US general population. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3-6 weeks. The outcome measure data is the mean of the data collected during the span of the measured time points.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=9 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=9 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Patient-reported Cognitive Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a)	53.8 score on a scale Standard Deviation 7.13	52.4 score on a scale Standard Deviation 7.61

SECONDARY outcome

Timeframe: The max amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, bi-weekly, end of period and intervention visits, and during follow-up.

The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a heart failure-specific health status survey. Questions are ranked on 5- to 7-point Likert scales, with higher scores indicating better health status. KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=9 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=9 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Patient-reported Health Status When on Beta-blocker Versus When Off Beta-blocker, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12)	58.7 score on a scale Standard Deviation 24.53	66.0 score on a scale Standard Deviation 17.36

SECONDARY outcome

Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

The EuroQol-5D Visual Analogue System (EQ-5D VAS) indicates patient-perceived health on a vertical visual analogue scale. The scale ranges from 0, indicating poorest health, to 100, indicating the best health. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's "home" dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame.

Outcome measures

Outcome measures
Measure	ON Beta Blockers n=9 Participants Subjects are on their standard of care beta-blocker dosage, which is the dosage that they were on when they enrolled into the trial.	OFF Beta Blockers n=9 Participants Subjects have been titrated off their standard of care beta-blocker dosage, and are now not on any beta-blocker.
Change in Patient-reported Health When on Beta-blocker Versus When Off Beta-blocker, as Measured by the EuroQol-5D Visual Analogue System (EQ-5D VAS)	68.9 score on a scale Standard Deviation 16.06	67.8 score on a scale Standard Deviation 17.20

Adverse Events

ON Beta Blockers

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

OFF Beta Blockers

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Subjects in Follow-Up

Serious events: 2 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	ON Beta Blockers n=9 participants at risk Subjects on their standard of care beta-blocker dosage (the dosage they were on when they enrolled in the trial).	OFF Beta Blockers n=9 participants at risk Subjects titrated off their standard-of-care beta-blocker dosage (not on any beta-blocker).	Subjects in Follow-Up n=9 participants at risk After completing their intervention phase, and deciding whether they prefer to continue or discontinue their beta-blocker, subjects proceed to a 12-month-long follow-up phase.
Cardiac disorders Heart Failure	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Cardiac disorders Cardiac Arrest	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Vascular disorders Hypotension	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 2 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.

Other adverse events

Other adverse events
Measure	ON Beta Blockers n=9 participants at risk Subjects on their standard of care beta-blocker dosage (the dosage they were on when they enrolled in the trial).	OFF Beta Blockers n=9 participants at risk Subjects titrated off their standard-of-care beta-blocker dosage (not on any beta-blocker).	Subjects in Follow-Up n=9 participants at risk After completing their intervention phase, and deciding whether they prefer to continue or discontinue their beta-blocker, subjects proceed to a 12-month-long follow-up phase.
Vascular disorders Hypertension	11.1% 1/9 • Number of events 4 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	22.2% 2/9 • Number of events 4 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 3 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Nervous system disorders Dizziness	33.3% 3/9 • Number of events 6 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Cardiac disorders Sinus Bradycardia	22.2% 2/9 • Number of events 3 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Vascular disorders Hypotension	55.6% 5/9 • Number of events 35 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	55.6% 5/9 • Number of events 38 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	22.2% 2/9 • Number of events 7 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Cardiac disorders Sinus Tachycardia	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	33.3% 3/9 • Number of events 3 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Eye disorders Eye disorders - other, specify	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
General disorders Fatigue	22.2% 2/9 • Number of events 5 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Cardiac disorders Palpitations	11.1% 1/9 • Number of events 2 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	22.2% 2/9 • Number of events 2 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Cardiac disorders Heart Failure	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Eye disorders Retinal Vascular Disorder	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Nervous system disorders Nervous System Disorders - Other, specify	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Eye disorders Retinopathy	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Psychiatric disorders Depression	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	0.00% 0/9 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.	11.1% 1/9 • Number of events 1 • During the intervention period, which can include up to 4 periods, with each period being up to 6 weeks, and through the follow-up period, which lasts for 1 year after the subject's end of intervention date. At each study visit, the investigator inquired about the occurrence of AE/SAEs since the last visit. Additionally, interim events history was collected during each weekly dose modification phone call, and during each follow-up call. Information to be collected includes event description, time of onset, clinician's assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.

Additional Information

Princess Osma

Weill Cornell Medicine

Phone: 646-962-5910

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Beta Blocker ABAB Sequence n=5 Participants This arm will follow an ABAB sequence. "A" representing ON beta blockers and "B" representing OFF beta blockers. Subjects in this arm will continue their home dose during the initial A period, they will then crossover into Period 2, where dose reduction will begin until they are off of beta blockers. After Period 2, the subjects have the option to decide if they want to be on or off their beta blocker and proceed with the Follow-Up Phase, or continue to Period 3 if they don't feel ready to make that decision to stay on or go off their beta blocker yet. During Period 3, they will restart beta-blockers, gradually uptitrating until reaching their home dose and finally during period 4, we will again conduct a dose reduction until off of beta blockers. Beta blockers: The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with 4 periods, each period lasting up to 6 weeks. During the On period (A), subjects will be on their beta blocker. During the Off period (B), their beta blockers will be down titrated and subsequently discontinued. Subjects will be randomized into either ABAB or BABA sequences.	Beta Blocker BABA Sequence n=4 Participants This arm will follow a BABA sequence. "A" representing ON beta blockers and "B" representing OFF of beta blockers. Subjects in this arm will have their previously prescribed beta blocker dose reduced until they are completely off of beta blockers during Period 1. They will then crossover into Period 2, where uptitration will begin until they are back on their previously prescribed dose of beta blockers. After Period 2, the subjects have the option to decide if they want to be on or off their beta blocker and proceed with the Follow-Up Phase, or continue to Period 3 if they don't feel ready to make that decision to stay on or go off their beta blocker yet. During Period 3, we will again conduct a dose reduction, until the subject is off of beta blockers and finally during Period 4, we will uptitrate them back to their home dose of beta blockers. Beta blockers: The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with 4 periods, each period lasting up to 6 weeks. During the On period (A), subjects will be on their beta blocker. During the Off period (B), their beta blockers will be down titrated and subsequently discontinued. Subjects will be randomized into either ABAB or BABA sequences.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants