Treatment With Higher Dosages of Heart Failure Medication Is Associated With Improved Outcome Following Cardiac Resynchronization Therapy

Study Questions:

What is the effect of chronic heart failure (CHF) medication dosage on morbidity and mortality in CHF patients after cardiac resynchronization therapy (CRT) implantation?


The study authors assessed CHF medication in 185 patients after CRT implantation. The medications included angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin-receptor blockers (ARBs), beta-blockers, spironolactone, loop diuretics, and digoxin. The primary combined endpoint was death, heart transplantation, assist device implantation, or hospitalization for CHF. The secondary endpoint of the study was death (from any cause), heart transplantation, or ventricular assist device implantation. The mean follow-up period was 44.6 months.


The study authors found that during the follow-up period, 83 patients experienced a primary endpoint. Therapy with higher dosages of ACE-I or ARBs (p = 0.001) and beta-blockers (p < 0.001) as well as with lower dosages of loop diuretics (p < 0.001) were associated with a reduced risk for the primary combined endpoint as well as for all-cause mortality. They found that super-responders (as determined by echocardiography) to CRT were treated with higher average dosages of ACE-I/ARBs (68.1 vs. 52.4%, p < 0.01) and beta-blockers (59 vs. 42.2%, p < 0.01). During follow-up, the average dosage of loop diuretics was decreased by 20% in super-responders, but increased by 30% in nonsuper-responders (p < 0.03).


The authors concluded that increasing neurohormonal blockade whenever possible following CRT implantation is desirable because of lower morbidity and mortality following CRT implantation.


This is an important study because it raises the question of whether CRT allows increase in doses of neurohormonal blockers (and therefore additive) or whether it is important to wait until maximum dose neurohormonal blockade is achieved before implanting CRT. Prospective studies are required to determine the relative efficacy of neurohormonal blockade and/or CRT. Regardless, this study suggests that after CRT implantation, it is important to continue to increase the dose of neurohormonal blockade until maximum dose have been attained. The decrease in diuretic response in super-responders is probably a reflection of better reverse remodeling in super-responders. Further studies are required to determine whether the higher mortality associated with a larger dose of diuretic therapy is a reflection of advanced disease or whether higher doses actually increase mortality.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support

Keywords: Angiotensin Receptor Antagonists, Follow-Up Studies, Digoxin, Heart-Assist Devices, Diuretics, Spironolactone, Sodium Potassium Chloride Symporter Inhibitors, Heart Transplantation, Cardiac Resynchronization Therapy, Heart Failure

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