A dose-response relationship for evidence-based beta-blockers used in HFrEF has been demonstrated (i.e., the higher the dose, the better the outcome) (27). Before initiating ivabradine, the dose of an evidence- based beta-blocker should be optimized and increased to the target dose as long as excessive bradycardia is not an issue. Some apparently well-compensated patients on optimal beta-blocker therapy continue to have a persis- tent resting heart rate over 70 beats/min, and some pa- tients do not tolerate up-titration of beta-blockade to the target dose and have an elevated heart r ate. 