High doses of beta-blockers can precipitate decompensation because they acutely reduce the heart’s compensatory sympathetic drive.

In a failing heart, cardiac output is often partly maintained by catecholamines acting at beta-1 receptors to increase:

A large or rapidly increased beta-blocker dose blocks these effects. This can cause:

So, early after initiation or dose escalation, the negative inotropic and chronotropic effects may outweigh benefit and cause worsening fatigue, edema, dyspnea, or low-output symptoms. Braunwald describes beta-blockers as having negative inotropic effects that can precipitate or worsen heart failure, particularly acutely. Braunwald’s Heart Disease, HEMODYNAMIC EFFECTS, p. 2478. Similarly, acute use can worsen HF in LV systolic dysfunction, hence the need for slow titration. Current Surgical Therapy 14e, β-Adrenergic Receptor Antagonists, pp. 2429-2435.

This does not mean beta-blockers are harmful in chronic HFrEF. At low doses with gradual up-titration in a euvolemic, hemodynamically stable patient, they reduce chronic catecholamine toxicity, improve LV remodeling and survival. A recent review notes beta-blockers should generally be started only after hemodynamic stabilization and that abrupt withdrawal can cause sympathetic rebound and worse outcomes (review of inpatient beta-blocker use).

Clinical takeaway: start low, increase slowly, and avoid initiating or aggressively increasing the dose during active congestion, hypoperfusion, cardiogenic shock, marked bradycardia, or symptomatic hypotension.