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The goal of this study is to test the feasibility of guiding as-needed pharmacological rate control of atrial fibrillation (AF) by implantable cardiac monitors and to assess the impact of continuous beta-blocker therapy versus as-needed rate control on the following outcomes:
(1) exercise capacity, (2) AF burden, (3) symptomatic heart failure, (4) biomarker assessment of cardiac filling pressures and cardio-metabolic health, and (5) quality of life in patients with atrial fibrillation and stage II or III heart failure with preserved ejection fraction.
Patients ≥ 18 years of age with paroxysmal or persistent AF who have an implantable cardiac monitor (either loop recorder or pacemaker) and who are receiving daily beta-blocker therapy will be screened for meeting the inclusion/exclusion criteria.
Trial participants will then be randomized into the daily beta-blocker or as-needed pharmacological rate control.
At baseline and six months trial participants will undergo assessment of the following measures:
Study participants may opt into long-term follow up visits at 12, 18 and 24 months.
Chart review will continue for up to 4 years after enrollment for the purpose of monitoring clinical endpoints:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | No Intervention | Patients randomized to the control arm will continue taking their daily beta-blocker for rate control of atrial fibrillation | |
| As needed rate control | Experimental | Patients randomized to the experimental arm will stop their daily beta-blocker and take as needed rate control guided by their implantable cardiac monitor |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| As needed pharmacological rate control with beta-blocker (metoprolol tartrate, metoprolol succinate) or calcium channel blocker (diltiazem, verapamil) | Drug | Patients will stop their daily beta-blocker and take as-needed rate control (beta-blocker or calcium channel blocker) guided by their implantable cardiac monitor |
| Measure | Description | Time Frame |
|---|---|---|
| Exercise capacity | Change in peak oxygen consumption during cardiopulmonary exercise testing | At time of randomization and 6 months afterwards. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with a composite of treatment related adverse events | Number of heart failure hospitalization, unplanned hospitalization for atrial fibrillation, stroke or transient ischemic attack, acute coronary syndrome in both treatment arms | At 6 months, at 12 months, at 18 months, at 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with a composite of treatment related heart failure events | Heart failure events: diuretic drug change, emergency room visit | At 6 months, at 12 months, at 18 months, at 24 months |
| Number of participants with a composite of treatment related atrial fibrillation events |
Inclusion Criteria:
Exclusion Criteria:
Minimum dosage of beta-blocker therapy to meet enrollment criterion:
Metoprolol tartrate 25mg twice daily, Metoprolol succinate 50mg daily, Carvedilol 12.5mg daily, Bisoprolol 5mg twice daily, Nebivolol 5mg daily, Atenolol 50mg daily, Labetalol 100mg twice daily, Propranolol 40mg twice daily
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nicole Habel, MD | Contact | 8028470000 | nicole.habel@uvmhealth.org | |
| Amy Henderson | Contact | amy.henderson@uvmhealth.org |
| Name | Affiliation | Role |
|---|---|---|
| Nicole Habel, MD | University of Vermont | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Vermont Medical Center | Recruiting | Burlington | Vermont | 05405 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29378762 | Background | Reddy YNV, Obokata M, Gersh BJ, Borlaug BA. High Prevalence of Occult Heart Failure With Preserved Ejection Fraction Among Patients With Atrial Fibrillation and Dyspnea. Circulation. 2018 Jan 30;137(5):534-535. doi: 10.1161/CIRCULATIONAHA.117.030093. No abstract available. | |
| 31525068 | Background | Meyer M, LeWinter MM. Heart Rate and Heart Failure With Preserved Ejection Fraction: Time to Slow beta-Blocker Use? Circ Heart Fail. 2019 Aug;12(8):e006213. doi: 10.1161/CIRCHEARTFAILURE.119.006213. Epub 2019 Aug 1. No abstract available. |
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|
Atrial fibrillation events: planned hospitalization, emergency room visit, cardioversion, antiarrhythmic medication initiation |
| At 6 months, at 12 months, at 18 months, at 24 months |
| Change in quality of life by Minnesota Living with heart failure questionnaire score | Score ranges from 0-105 with higher scores meaning worse quality of life | At time of randomization and 6 months afterwards. |
| Change in quality of life by Atrial fibrillation Effect on Quality of life questionnaire score | Score ranges from 0-100 with higher scores meaning better quality of life | At time of randomization and 6 months afterwards. |
| Change in NTproBNP | At time of randomization and 6 months afterwards. |
| Change in hsTroponin | At time of randomization and 6 months afterwards. |
| Change in HbA1c | At time of randomization and 6 months afterwards. |
| Change in Fructosamine | At time of randomization and 6 months afterwards. |
| Change in Cystatin C | At time of randomization and 6 months afterwards. |
| Change in atrial fibrillation burden recorded by implantable cardiac monitor | At time of randomization and 6 months afterwards. |
| Change in 6 minute walk distance | At time of randomization and 6 months afterwards. |
| Change in device detected activity level | At time of randomization and 6 months afterwards. |
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| 32860505 | Background | Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 Feb 1;42(5):373-498. doi: 10.1093/eurheartj/ehaa612. No abstract available. |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000319 | Adrenergic beta-Antagonists |
| D008790 | Metoprolol |
| D002121 | Calcium Channel Blockers |
| D004110 | Diltiazem |
| D014700 | Verapamil |
| ID | Term |
|---|---|
| D018674 | Adrenergic Antagonists |
| D018663 | Adrenergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D049990 | Membrane Transport Modulators |
| D000077264 | Calcium-Regulating Hormones and Agents |
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
Not provided
Not provided