title: Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes.
  
  
  RESULTS
  Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709).
  
  
  CONCLUSIONS
  After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation.
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Martens
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.
authors.forename: Frederik H
authors.initials: FH
authors.lastname: Verbrugge
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Nijst
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Philippe B
authors.initials: PB
authors.lastname: Bertrand
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dupont
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium. Electronic address: Wilfried.Mullens@zol.be.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Mullens
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents
keywords: Cardiac resynchronization therapy; neurohumoral-blockers; outcome; quality of care