Atrial Fibrillation, Diastolic Dysfunction, HFpEF - Heart Failure With Preserved Ejection Fraction
Conditions
Keywords
AF, HFpEF, Exercise capacity, Peak oxygen consumption, Beta Blocker
Brief summary
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.
Detailed description
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: * Assessment of Quality of life using the Minnesota Living with Heart Failure Questionnaire and the Atrial Fibrillation Effect on Quality of life Questionnaire. * Blood draw * Cardiopulmonary exercise test, 6 Minute Walk Test and average daily activity level via integrated accelerometer of the implantable cardiac monitor (if available). * Assessment of AF burden 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: * Heart failure events (diuretic drug change, emergency room visit, hospitalization) * AF events (hospitalization, emergency room visit, cardioversion, antiarrhythmic medication initiation) * Stroke or transient ischemic attack * Myocardial infarction
Interventions
DRUGAs needed pharmacological rate control with beta-blocker (metoprolol tartrate, metoprolol succinate) or calcium channel blocker (diltiazem, verapamil)
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
Sponsors
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Paroxysmal or persistent AF diagnosed in the past 4 weeks or longer * Implantable cardiac monitor (either loop recorder or pacemaker) * Current treatment with greater than minimum doses of beta-blockers OR any beta-blocker with resting sinus rhythm heart rate \< 75 bpm (documented on EKG in the last 6 months OR at enrollment visit) * Left ventricular ejection fraction ≥ 50% (reported on echocardiogram within the past 48 months) * Echocardiographic evidence of structural changes consistent with HFpEF defined by (1) left ventricular hypertrophy (septal or posterior wall thickness \> 10mm) OR (2) left atrial enlargement OR (3) diastolic dysfunction.
Exclusion criteria
* Long-standing persistent or permanent atrial fibrillation (Long-standing persistent AF is defined as continuous AF of \> 12 months duration. Permanent AF is defined as AF accepted by the patient and physician and no further attempts to restore/maintain sinus rhythm will be undertaken). * Echocardiographic evidence of left ventricular dilation (defined as left ventricular end diastolic volume (LVEDV) index ≥ 80ml/m2 as determined by echocardiogram within the past 48 months. * Documentation in the electronic medical record suggesting a life expectancy less than 12 months 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise capacity | At time of randomization and 6 months afterwards. | Change in peak oxygen consumption during cardiopulmonary exercise testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with a composite of treatment related adverse events | At 6 months, at 12 months, at 18 months, at 24 months | Number of heart failure hospitalization, unplanned hospitalization for atrial fibrillation, stroke or transient ischemic attack, acute coronary syndrome in both treatment arms |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in quality of life by Minnesota Living with heart failure questionnaire score | At time of randomization and 6 months afterwards. | Score ranges from 0-105 with higher scores meaning worse quality of life |
| Change in quality of life by Atrial fibrillation Effect on Quality of life questionnaire score | At time of randomization and 6 months afterwards. | Score ranges from 0-100 with higher scores meaning better quality of life |
| 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. | — |
| Number of participants with a composite of treatment related heart failure events | At 6 months, at 12 months, at 18 months, at 24 months | Heart failure events: diuretic drug change, emergency room visit |
| 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. | — |
| Change in Fructosamine | At time of randomization and 6 months afterwards. | — |
| Number of participants with a composite of treatment related atrial fibrillation events | At 6 months, at 12 months, at 18 months, at 24 months | Atrial fibrillation events: planned hospitalization, emergency room visit, cardioversion, antiarrhythmic medication initiation |
Countries
United States
Contacts
Primary ContactNicole Habel, MD
Backup ContactAmy Henderson
Outcome results
None listed