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The study will include patients with acute heart failure with reduced left ventricular ejection fraction (<40%) triggered by atrial fibrillation (AF) with a heart rate of >130/min. Patients in cardiogenic shock, critical state, or patients requiring emergent electric cardioversion during the first 2 hours will be excluded. The patients will be randomized (1:1) to a strategy of initial intensive heart rate control using continuous infusion of landiolol and boluses of digoxin vs. standard approach to the rate control without the use of landiolol. All patients will receive recommended pharmacotherapy of acute heart failure (diuretics, nitrates, inotropes in patients with signs of low cardiac output - preferentially milrinone or levosimendan). The patients will undergo hemodynamic monitoring, laboratory testing, evaluation of symptoms, and quantification of lung water content by ultrasound for 48 hours. The study will test a hypothesis whether patients treated with initial intensive heart rate control with the preferential use of landiolol will achieve faster heart rate control, compensation of heart failure, and relief of heart failure symptoms without causing hypotension or deterioration of heart failure.
Procedure:
Eligible patients with signed consent will be enrolled.
Baseline transthoracic echocardiography, laboratory testing, evaluation of subjective dyspnea, lung water by ultrasound, chest x-ray, hemodynamic monitoring (details below)
Randomisation 1:1 to standard therapy vs. intensive heart rate control
Two hours of therapy with continous hemodynamic monitoring (blood pressure by arterial line, cardiac output and stroke volume non-invasively by bioreactance)
At 2 hours: evaluation of patients subjective dyspnea (primary clinical endpoint), heart rate (primary endpoint), hearth rhythm and hemodynamics
After 2 hours, both groups can be treated according to the preference of the physician.
Symptoms, heart rate control, hemodynamics and lung congestion will be reevaluated at 12 and 48 hours
The study protocol will end after 48 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intensive rate control with landiolol | Experimental | Intensive heart rate control using landiolol with the goal to achieve HR<115 during the first 2 hours. |
|
| Standard therapy | Active Comparator | Standard heart rate control with therapy other than landiolol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intensive heart rate control with landiolol | Drug | Intensive heart rate control preferably with the use of short-acting betablocker landiolol in combination with digoxin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Heart rate control | Achievement of heart rate <115/min for at least 15 mins | during the first 2 hours |
| Change in patient-reported symptoms | Change of patient-reported dyspnea evaluated 1-10 visual analog scale (1=unbearable dyspnea, 10=no symptoms) | at 2 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Significant change of heart rate | Decrease of heart rate >20% from baseline | During the first 2 hours |
| Heart rate and heart rhythm | the mean heart rate obtained from three measurements |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marek Sramko, MD., PhD. | Contact | +420776246127 | marek.sramko@ikem.cz |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Clinical and Experimental Medicine (IKEM) | Recruiting | Prague | 14021 | Czechia |
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Patients will be randomized 1:1 to intensive rate control with landiolol vs. standard therapy
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|
| Standard approach to heart rate control | Drug | Standard heart rate control with intravenous or oral beta-blockers and/or antiarrhythmic in combination with digoxin |
|
| heart rate measured at hours 2, 12 and 48 of the study protocol |
| Safety - hypotension | Occurence of hypotension requiring reduction of the dose of betablockers or vasopressors | first 2 hours |
| Change in cardiac index | Change in cardiac index (L/m2) evaluated noninvasively by bioreactance (Starling SV, Cheetah Medical) | evaluated between baseline and hour 2 |
| Change in stroke volume index | Change in stroke volume index (ml/m2) evaluated noninvasively by bioreactance (Starling SV, Cheetah Medical) | evaluated between baseline and hour 2 |
| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D018487 | Ventricular Dysfunction, Left |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018754 | Ventricular Dysfunction |
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| ID | Term |
|---|---|
| C077049 | landiolol |
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