Amendment 1 changes: -AF Burden substudy has been modified. -The requirement for a third rhythm assessment 7-9 days after the initial AF event for the classification of paroxysmal/persistent AF has been removed. -The AFSQ previously required at the time of the ECG/TTM assessment for the determination of paroxysmal/persistent AF was removed. -Clarification has been provided on the use of concomitant and prohibited medications allowed during the study. -Text has been added to clarify that a trough blood sample for the Population PK substudy only needs to be collected at Visit 3 for patients who spontaneously convert to SR. -Two additional genes have been included in the required genetic analysis to explore the potential for polymorphisms in these genes to alter the effectiveness of bucindolol. -The management of patient visits during the Drug Lead-In Period has been modified to emphasize that unscheduled visits should be used to manage study drug titration prior to ECV at Visit 3. -The estimate for the number of investigational sites participating in the Phase 3 portion of the trial has been updated. -The stratification criterion for randomization, “type of Medtronic device (Reveal/Non-Reveal/No Device)”, has been clarified. -The protocol has been updated to emphasize that vital status (i.e., alive/dead) will be assessed periodically during the study, including for patients who withdraw from the study who consent to periodic telephone contact. -inclusion/exclusion criteria updated. -endpoints have been modified. -up-titration schedule has been modified -optional substudies and schedule of assessments have been modified or clarified.

Expansion of the participant population to include participants in SR at randomization with a recent episode of symptomatic AF Randomization stratum added to ensure balance between the 2 treatment arms for participants in SR at randomization and participants in AF at randomization Stable SR definition for primary endpoint adjusted to reflect new population Additional language added to the protocol to clarify when ECV should be performed Modified requirements for early ECV (i.e., earlier than 3 weeks after randomization) have to ensure that participants are receiving therapeutic doses of study drug prior to ECV Additional information provided regarding the timing of study drug dosing on the day of randomization and on the requirement for titration of study drug dose to protocol-specified targets Study drug transition algorithm updated to include guidance for immediate release metoprolol, controlled release carvedilol, and bisoprolol LVIDD requirement for participants with LVEF between 0.40 and 0.50 deleted Study entry criterion that defines the exclusion period for previous AF ablation modified Malignancy exclusion criteria clarified Several inclusion and exclusion criteria modified to be effective at the randomization visit instead of at the screening visit Modified timing of clinical visits during the 24-week follow-up period to occur every 4 weeks, altheranaing with at-home TTM Modified timing of required second ECG to at least 10 minutes after the first ECG recording if AF/AFL is observed on the first assessment from 1 hour Streamlined AF symptom questionnaire and device interrogation administration for greater consistency Collections schedule for several clinical laboratory tests modified to limit the number of separate phlebotomy procedures Participation in the population pharmacokinetic analysis made mandatory Sample size justification updated to reference the EURIDIS/ADONIS dronedarone AF studies

Primary efficacy endpoint definition of stable SR changed to SR on rhythm assessments at least 1 hour apart at Week 0 or 1 hour after ECV. Supportive secondary efficacy endpoint analysis has been added for hospitalizations: the subset of HF-related hospitalization Updated statistical methodology for several tertiary/exploratory efficacy endpoints and AF burden definition in the device substudy Interim analyses: Phase 2B interim analysis details relocated to DSMB charter. new Phase 3 interim analysis added to assess the absence of futility and whether an expansion of the total sample size is warranted Updated description of study drug packaging Updated study drug titration schedule table to provide guidance for the transition from the β-blocker nebivolol to blinded study drug Concomitant administration of 2 anti-arrhythmic drugs (i.e., flecainide and propafenone) is no longer permitted due to the potential for CYP2D6-mediated drug interactions with study drug Sample size for Phase 2B changed from 200 to 250 participants Inclusion and exclusion criteria updated: upper age limit of 85 years added; minimum weight requirement changed from screening to randomization visit; qualifying LVEF assessment anytime during previous 12 months; window for qualifying AF episode enlarged from 120 to 180 days before screening; modifications to criteria of timing of ECV, clinical euvolemia, informed consent, β-blocker contraindications, lab value retesting; new exclusion criteria added for left ventricular assist devices, symptomatic bradycardia, and pulmonary hypertension. Concomitant medication criteria modified to only exclude frequent use of short acting nitroglycerine for the treatment of acute angina; prophylactic use of sustained release nitroglycerine for the prevention of angina is not exclusionary The maximum time period between the screening visit and the randomization visit has been increased from 4 to 8 weeks to allow additional time