Impact of Optimized Pacing Strategies on Clinical and Hemodynamic Outcomes in Heart Failure Patients With Pacemaker

Official title

Clinical and Hemodynamic Outcomes of OPTimized PACing StratEgies in Heart Failure Patients With Pacing Indications: Randomized-Controlled Trial (OPTPACE-HF)

Overview

This study aims to evaluate the clinical impact of an optimized pacing strategy in patients with heart failure. * Intervention: Adjustment of the pacemaker lower rate limit to an individualized, hemodynamically optimized heart rate. * Primary Endpoint: Heart failure symptoms, assessed by the Kansas City Cardiomyopathy Questionnaire score. * Hypothesis: In patients with heart failure requiring permanent pacing, an optimized pacing strategy will lead to a significant improvement in heart failure symptoms (Kansas City Cardiomyopathy Questionnaire score) at 12 months compared with the conventional pacing strategy.

Detailed description

Heart failure is a growing health concern with increasing prevalence in the aging population, and permanent pacemaker implantation is frequently required due to concomitant bradyarrhythmias. Heart rate is closely associated with hemodynamic status in patients with heart failure; however, evidence guiding the optimal pacemaker lower rate setting remains limited. Although the conventional lower rate is typically set at 50-60 bpm, recent studies suggest that a moderately increased pacing rate may improve hemodynamics and clinical outcomes. Furthermore, advances in physiological pacing techniques, such as conduction system pacing, provide the potential for greater clinical benefits through optimized heart rate settings in this patient population.

Enrolled subjects are randomized in a 1:1 ratio into either the optimized pacing group or the conventional pacing strategy group based on stratification factors.

The optimized pacing group undergoes post-procedural right heart catheterization with adjustments to the lower rate limit, where the heart rate (HR) that yields the lowest mean pulmonary capillary wedge pressure (mPCWP) or the highest cardiac output is determined as the optimal HR. In the conventional pacing strategy group, the lower rate limit is set at 60 bpm. Clinical symptoms and parameters of both groups are subsequently compared over a one-year follow-up period.

Interventions

• Procedure Adjustment of the pacemaker/ICDs lower rate limit (LRL)
  Optimized Pacing Strategy
• Procedure Conventional lower rate (60bpm)
  Conventional Pacing Strategy

Primary outcome measures

• Kansas City Cardiomyopathy Questionnaire [Time frame: From enrollment to 1year after the procedure]

Secondary outcome measures (12)

• NTproBNP [Time frame: From enrollment to 1year after the procedure]
• Functional status (NYHA class) [Time frame: From enrollment to 1year after the procedure]
• Distance in 6-minute walk test [Time frame: From enrollment to 1year after the procedure]
• Occurrence of atrial fibrillation [Time frame: From enrollment to 1year after the procedure]
• Atrial fibrillation burden [Time frame: From enrollment to 1year after the procedure]
• Invasive hemodynamics parameters in right heart catheterization [Time frame: At the time of CIED implantation]
• CIED Battery longevity [Time frame: From enrollment to 1year after the procedure]
• All-cause mortality [Time frame: From enrollment to 1year after the procedure]
• Cardiac mortality [Time frame: From enrollment to 1year after the procedure]
• Re-hospitalization due to all cause [Time frame: From enrollment to 1year after the procedure]
• Hospitalization due to heart failure [Time frame: From enrollment to 1year after the procedure]
• Average heart rate [Time frame: From enrollment to 1year after the procedure]

Eligibility criteria

Inclusion criteria

• Patients with symptomatic bradycardia who meet the indication for permanent pacemaker implantation and fulfill one of the following conditions:

• Sick sinus syndrome with or without impaired atrioventricular conduction
• Persistent or permanent atrial fibrillation with slow ventricular response
• Chronotropic incompetence
• Patients diagnosed with heart failure with left ventricular ejection fraction ≥ 50% on transthoracic echocardiography with at least one of the following:
• H2FPEF score ≥ 6 or HFA-PEFF score ≥ 5
• N-terminal pro-B-type natriuretic peptide ≥ 300 pg/mL (sinus rhythm) or ≥ 600 pg/mL (atrial fibrillation)
• Prior hospitalization for heart failure or documented use of loop diuretics for heart failure symptoms

Exclusion criteria

• Patients expected to have a ventricular pacing burden ≥ 20% without sufficient capture of cardiac physiologic pacing, which includes biventricular pacing, His bundle pacing, and left bundle branch area pacing.

(Sufficient cardiac physiologic pacing is defined as a paced QRS duration ≤ 140 ms.)

• Patients not expected to achieve sufficient pacing dependency, defined as:

• In sinus rhythm: baseline atrial rate > 60 bpm on Holter monitoring or inpatient ECG monitoring
• In atrial fibrillation/flutter: baseline ventricular rate > 60 bpm on Holter monitoring or inpatient ECG monitoring
• Patients with contraindications to permanent pacemaker implantation
• Patients with moderate or greater valvular stenosis or regurgitation.
• Patients with dyspnea not attributable to heart failure, due to uncontrolled comorbid conditions
• Pregnant or breastfeeding women.
• Patients who have refused active treatment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center — Seoul

Publications

• Bozkurt B, Colvin M, Cook J, Cooper LT, Deswal A, Fonarow GC, Francis GS, Lenihan D, Lewis EF, McNamara DM, Pahl E, Vasan RS, Ramasubbu K, Rasmusson K, Towbin JA, Yancy C; American Heart Association Committee on Heart Failure and Transplantation of the Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Epidemiolo PMID 27832612
• van Loon T, Rijks J, van Koll J, Wolffs J, Cornelussen R, van Osta N, Luermans J, Prinzen F, Linz D, van Empel V, Delhaas T, Vernooy K, Lumens J. Accelerated atrial pacing reduces left-heart filling pressure: a combined clinical-computational study. Eur Heart J. 2024 Dec 7;45(46):4953-4964. doi: 10.1093/eurheartj/ehae718. PMID 39589540
• Infeld M, Wahlberg K, Cicero J, Plante TB, Meagher S, Novelli A, Habel N, Krishnan AM, Silverman DN, LeWinter MM, Lustgarten DL, Meyer M. Effect of Personalized Accelerated Pacing on Quality of Life, Physical Activity, and Atrial Fibrillation in Patients With Preclinical and Overt Heart Failure With Preserved Ejection Fraction: The myPACE Randomized Clinical Trial. JAMA Cardiol. 2023 Mar 1;8(3):21 PMID 36723919
• Hernandez AF, Hammill BG, O'Connor CM, Schulman KA, Curtis LH, Fonarow GC. Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) Registry. J Am Coll Cardiol. 2009 Jan 13;53(2):184-92. doi: 10.1016/j.jacc.2008.09.031. PMID 19130987
• Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Jacobs AK, Hiratzka LF, Russell RO, Smith SC Jr; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 199 PMID 11739319
• Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). J Am Coll Cardiol. 1995 Nov 1;26(5):1376-98. No abstract available. PMID 7594057
• Wachter R, Schmidt-Schweda S, Westermann D, Post H, Edelmann F, Kasner M, Luers C, Steendijk P, Hasenfuss G, Tschope C, Pieske B. Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure. Eur Heart J. 2009 Dec;30(24):3027-36. doi: 10.1093/eurheartj/ehp341. PMID 19720638
• Kotecha D, Flather MD, Altman DG, Holmes J, Rosano G, Wikstrand J, Packer M, Coats AJS, Manzano L, Bohm M, van Veldhuisen DJ, Andersson B, Wedel H, von Lueder TG, Rigby AS, Hjalmarson A, Kjekshus J, Cleland JGF; Beta-Blockers in Heart Failure Collaborative Group. Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure. J Am Coll Cardiol. 2017 Jun 20;69(24):2885-2896. PMID 28467883

Identifiers

NCT: NCT07563153 · SMC 2025-05-136 · KCT0010987

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗