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Article ; Online: Comments on the myPACE Randomized Clinical Trial-Reply.

Infeld, Margaret / Lustgarten, Daniel L / Meyer, Markus

JAMA cardiology

2023 Volume 8, Issue 8, Page(s) 795

Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2380-6591
ISSN (online)	2380-6591
DOI	10.1001/jamacardio.2023.1746
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Article: Personalized accelerated physiologic pacing.

Meyer, Markus / Infeld, Margaret / Habel, Nicole / Lustgarten, Daniel

European heart journal supplements : journal of the European Society of Cardiology

2023 Volume 25, Issue Suppl G, Page(s) G33–G43

Abstract: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent with a high socioeconomic burden. Pharmacological heart rate lowering was recommended to improve ventricular filling in HFpEF. This article discusses the misperceptions that ...

Abstract	Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent with a high socioeconomic burden. Pharmacological heart rate lowering was recommended to improve ventricular filling in HFpEF. This article discusses the misperceptions that have resulted in an overprescription of beta-blockers, which in all likelihood have untoward effects on patients with HFpEF, even if they have atrial fibrillation or coronary artery disease as a comorbidity. Directly contradicting the lower heart rate paradigm, faster heart rates provide haemodynamic and structural benefits, amongst which lower cardiac filling pressures and improved ventricular capacitance may be most important. Safe delivery of this therapeutic approach is feasible with atrial and ventricular conduction system pacing that aims to emulate or enhance cardiac excitation to maximize the haemodynamic benefits of accelerated pacing. This conceptual framework was first tested in the myPACE randomized controlled trial of patients with pre-existing pacemakers and preclinical or overt HFpEF. This article provides the background and path towards this treatment approach.
Language	English
Publishing date	2023-11-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1463769-8
ISSN	1554-2815 ; 1520-765X
ISSN (online)	1554-2815
ISSN	1520-765X
DOI	10.1093/eurheartjsupp/suad117
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Zs.A 1563 -Suppl.-: Show issues

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Article ; Online: Rationale and design of the PACE HFpEF trial: Physiologic accelerated pacing as a holistic treatment of heart failure with preserved ejection fraction.

Habel, Nicole / Infeld, Margaret / Bernknopf, Jacob / Meyer, Markus / Lustgarten, Daniel

Heart rhythm O2

2023 Volume 5, Issue 1, Page(s) 41–49

Abstract: Background: In heart failure with preserved ejection fraction (HFpEF), it has been assumed that pharmacologic heart rate suppression should provide clinical benefits through an increase in diastolic filling time. Contrary to this assumption, heart rate ... ...

Abstract	Background: In heart failure with preserved ejection fraction (HFpEF), it has been assumed that pharmacologic heart rate suppression should provide clinical benefits through an increase in diastolic filling time. Contrary to this assumption, heart rate lowering in patients with preserved left ventricular ejection fraction and hypertension or coronary artery disease results in adverse outcomes and suggests that the opposite may be beneficial. Namely, shortening the diastolic filling time with a higher heart rate might normalize the elevated filling pressures that are the Objective: The study sought to determine the effects of continued resting heart rate elevation with and without superimposed nocturnal pacing in HFpEF patients without standard pacing indication. Methods: The physiologic accelerated pacing as treatment for heart failure with preserved ejection fraction (PACE HFpEF) trial is an investigator-initiated, prospective, patient-blinded multiple crossover pilot study that assesses the impact of accelerated pacing on quality of life, physical activity, N-terminal pro-B-type natriuretic peptide, and echocardiographic measures of cardiac structure and function. Results: Twenty patients were enrolled and underwent dual-chamber pacemaker implantation under U.S. Food and Drug Administration investigational device exemption with both atrial and ventricular physiologic lead placement targeting the Bachmann bundle and the His bundle. Conclusion: This manuscript describes the rationale and design of the PACE HFpEF trial, which tests the safety and feasibility of continuous accelerated physiological pacing as a treatment strategy in HFpEF.
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ISSN	2666-5018
ISSN (online)	2666-5018
DOI	10.1016/j.hroo.2023.12.001
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Article ; Online: Effect of paced heart rate on quality of life and natriuretic peptides for stage B or C heart failure with preserved ejection fraction: A secondary analysis of the myPACE trial.

de la Espriella, Rafael / Wahlberg, Kramer J / Infeld, Margaret / Palau, Patricia / Núñez, Eduardo / Sanchis, Juan / Meyer, Markus / Núñez, Julio

European journal of heart failure

2024 Volume 26, Issue 1, Page(s) 167–176

Abstract: Aim: Emerging evidence suggests a beneficial effect of higher heart rates in some patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the impact of higher backup pacing rates in HFpEF patients with ... ...

Abstract	Aim: Emerging evidence suggests a beneficial effect of higher heart rates in some patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the impact of higher backup pacing rates in HFpEF patients with preexisting pacemaker systems that limit pacemaker-mediated dyssynchrony across left ventricular (LV) volumes and LV ejection fraction (LVEF). Methods and results: This is a post-hoc analysis of the myPACE clinical trial that evaluated the effects of personalized accelerated pacing setting (myPACE) versus standard of care on changes in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-brain natriuretic peptide (NT-proBNP), pacemaker-detected activity levels, and atrial fibrillation (AF) burden in patients with HFpEF with preexisting pacemakers. Between-treatment comparisons were performed using linear regression models adjusting for the baseline value of the exposure (ANCOVA design). This study included 93 patients with pre-trial transthoracic echocardiograms available (usual care n = 49; myPACE n = 44). NT-proBNP levels and MLHFQ scores improved in a higher magnitude in the myPACE group at lower indexed LV end-diastolic volumes (iLVEDV) (NT-proBNP-iLVEDV interaction p = 0.006; MLHFQ-iLVEDV interaction p = 0.068). In addition, personalized accelerated pacing led to improved changes in activity levels and NT-proBNP, especially at higher LVEF (activity levels-LVEF interaction p = 0.009; NT-proBNP-LVEF interaction p = 0.058). No evidence of heterogeneity was found across LV volumes or LVEF for pacemaker-detected AF burden. Conclusions: In the post-hoc analysis of the myPACE trial, we observed that the benefits of a personalized accelerated backup pacing on MLHFQ score, NT-proBNP, and pacemaker-detected activity levels appear to be more pronounced in patients with smaller iLVEDV and higher LVEF.
MeSH term(s)	Humans ; Atrial Fibrillation/complications ; Biomarkers ; Heart Failure/drug therapy ; Heart Rate ; Natriuretic Peptide, Brain/therapeutic use ; Peptide Fragments/therapeutic use ; Quality of Life ; Stroke Volume/physiology ; Ventricular Function, Left/physiology
Chemical Substances	Biomarkers ; Natriuretic Peptide, Brain (114471-18-0) ; Peptide Fragments
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Clinical Trial ; Journal Article
ZDB-ID	1483672-5
ISSN	1879-0844 ; 1388-9842
ISSN (online)	1879-0844
ISSN	1388-9842
DOI	10.1002/ejhf.3107
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Zs.A 5299: Show issues

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Article ; Online: Lower heart rates and beta-blockers are associated with new-onset atrial fibrillation.

Habel, Nicole / du Fay de Lavallaz, Jeanne / Infeld, Margaret / Koehler, Jodi L / Ziegler, Paul D / Lustgarten, Daniel L / Meyer, Markus

International journal of cardiology. Cardiovascular risk and prevention

2023 Volume 17, Page(s) 200182

Abstract: Background: Lower heart rates (HRs) prolong diastole, which increases filling pressures and wall stress. As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers may ...

Abstract	Background: Lower heart rates (HRs) prolong diastole, which increases filling pressures and wall stress. As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers may increase the risk for AF due to suppression of resting HRs. Objective: Examine the relationships of HR, BNP, beta-blockers and new-onset AF in the REVEAL-AF and SPRINT cohort of subjects at risk for developing AF. Methods: In REVEAL-AF, 383 subjects without a history of AF and a mean CHA Results: The median daytime HR in the REVEAL-AF cohort was 75bpm [IQR 68-83]. Subjects with below-median HRs had 2.4-fold higher BNP levels compared to subjects with above-median HRs (median BNP [IQR]: 62 pg/dl [37-112] vs. 26 pg/dl [13-53], p < 0.001). HRs <75bpm were associated with a higher incidence of AF: 37% vs. 27%, p < 0.05. This was validated in the SPRINT cohort after adjusting for AF risk factors. Both a HR < 75bpm and beta-blocker use were associated with a higher rate of AF: 1.9 vs 0.7% (p < 0.001) and 2.5% vs. 0.6% (p < 0.001), respectively. The hazard ratio for patients on beta-blockers to develop AF was 3.72 [CI 2.32, 5.96], p < 0.001. Conclusions: Lower HRs are associated with higher BNP levels and incident AF, mimicking the hemodynamic effects of diastolic dysfunction. Suppression of resting HR by beta-blockers could explain their association with incident AF.
Language	English
Publishing date	2023-02-25
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-4875
ISSN (online)	2772-4875
DOI	10.1016/j.ijcrp.2023.200182
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Article ; Online: Effects of Continuous Accelerated Pacing on Cardiac Structure and Function in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the myPACE Randomized Clinical Trial.

Wahlberg, Kramer J / Infeld, Margaret / Plante, Timothy B / Novelli, Alexandra E / Habel, Nicole / Burkhoff, Daniel / Barrett, Trace / Lustgarten, Daniel / Meyer, Markus

Journal of the American Heart Association

2023 Volume 13, Issue 1, Page(s) e032873

Abstract: Background: Heart failure with preserved ejection fraction ≥50% is prevalent with few evidence-based therapies. In a trial of patients with heart failure with preserved ejection fraction with specialized pacemakers, treatment with accelerated ... ...

Abstract	Background: Heart failure with preserved ejection fraction ≥50% is prevalent with few evidence-based therapies. In a trial of patients with heart failure with preserved ejection fraction with specialized pacemakers, treatment with accelerated personalized pacing averaging 75 bpm (myPACE) markedly improved quality of life, NT-proBNP (N-terminal pro-brain natriuretic peptide), physical activity, and atrial fibrillation burden compared with the standard lower rate setting of 60 bpm (usual care). Methods and results: In this exploratory study, provider-initiated echocardiographic studies obtained before and after the trial were assessed for changes in left ventricular (LV) structure and function among participants who continued their pacing assignment. The analytic approach aimed to detect differences in standard and advanced echocardiographic parameters within and between study arms. Of the 100 participants, 16 myPACE and 20 usual care arm had a qualifying set of echocardiograms performed a mean (SD) 3 (2.0) years apart. Despite similar baseline echocardiogram measures, sustained exposure to moderately accelerated pacing resulted in reduced septal wall thickness (in cm: myPACE 1.1 [0.2] versus usual care 1.2 [0.2], Conclusions: Exposure to continuous accelerated pacing in heart failure with preserved ejection fraction is associated with a reduced LV wall thickness and a small amount of LV dilation with small reduction in ejection fraction.
MeSH term(s)	Humans ; Atrial Fibrillation/therapy ; Heart Failure/diagnostic imaging ; Heart Failure/therapy ; Natriuretic Peptide, Brain ; Peptide Fragments ; Quality of Life ; Stroke Volume ; Ventricular Function, Left
Chemical Substances	Natriuretic Peptide, Brain (114471-18-0) ; Peptide Fragments
Language	English
Publishing date	2023-12-29
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.032873
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Article ; Online: Beta-Blocker Use and Heart Failure Outcomes in Mildly Reduced and Preserved Ejection Fraction.

Arnold, Suzanne V / Silverman, Daniel N / Gosch, Kensey / Nassif, Michael E / Infeld, Margaret / Litwin, Sheldon / Meyer, Markus / Fendler, Timothy J

JACC. Heart failure

2023 Volume 11, Issue 8 Pt 1, Page(s) 893–900

Abstract: Background: Although studies consistently show that beta-blockers reduce morbidity and mortality in patients with reduced ejection fraction (EF), data are inconsistent in patients with heart failure with mildly reduced ejection fraction (HFmrEF) and ... ...

Abstract	Background: Although studies consistently show that beta-blockers reduce morbidity and mortality in patients with reduced ejection fraction (EF), data are inconsistent in patients with heart failure with mildly reduced ejection fraction (HFmrEF) and suggest potential negative effects in heart failure with preserved ejection fraction (HFpEF). Objectives: The purpose of this study was to examine the association of beta-blockers with heart failure (HF) hospitalization and death in patients with HF and EF ≥40% METHODS: Beta-blocker use was assessed at first encounter in outpatients ≥65 years of age with HFmrEF and HFpEF in the U.S. PINNACLE Registry (2013-2017). The associations of beta-blockers with HF hospitalization, death, and the composite of HF hospitalization/death were assessed using propensity-score adjusted multivariable Cox regression models, including interactions of EF × beta-blocker use. Results: Among 435,897 patients with HF and EF ≥40% (HFmrEF, n = 75,674; HFpEF = 360,223), 289,377 (66.4%) were using a beta-blocker at first encounter; more commonly in patients with HFmrEF vs HFpEF (77.7% vs 64.0%; P < 0.001). There were significant interactions between EF × beta-blocker use for HF hospitalization, death, and composite of HF hospitalization/death (P < 0.001 for all), with higher risk with beta-blocker use as EF increased. Beta-blockers were associated with decreased risk of HF hospitalization and death in patients with HFmrEF but a lack of survival benefit and a higher risk of HF hospitalization in patients with HFpEF, particularly when EF was >60%. Conclusions: In a large, real-world, propensity score-adjusted cohort of older outpatients with HF and EF ≥40%, beta-blocker use was associated with a higher risk of HF hospitalization as EF increased, with potential benefit in patients with HFmrEF and potential risk in patients with higher EF (particularly >60%). Further studies are needed to understand the appropriateness of beta-blocker use in patients with HFpEF in the absence of compelling indications.
MeSH term(s)	Humans ; Heart Failure/drug therapy ; Stroke Volume ; Prognosis ; Registries ; Adrenergic beta-Antagonists/therapeutic use ; Hospitalization
Chemical Substances	Adrenergic beta-Antagonists
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2705621-1
ISSN	2213-1787 ; 2213-1779
ISSN (online)	2213-1787
ISSN	2213-1779
DOI	10.1016/j.jchf.2023.03.017
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Article: Left Atrial Appendage Closure: A Safe and Effective Alternative to Anticoagulation?

Infeld, Margaret M / Silverman, Daniel N / Lustgarten, Daniel L

The Journal of innovations in cardiac rhythm management

2019 Volume 10, Issue 1, Page(s) 3486–3493

Abstract: To date, left atrial appendage closure (LAAC) devices continue to be assessed as an intuitive alternative to oral anticoagulant therapy to prevent embolic complications in patients with atrial fibrillation. Concerns remain about the up-front risks ... ...

Abstract	To date, left atrial appendage closure (LAAC) devices continue to be assessed as an intuitive alternative to oral anticoagulant therapy to prevent embolic complications in patients with atrial fibrillation. Concerns remain about the up-front risks associated with device implantation as well as device efficacy in preventing embolic events as compared with anticoagulation. Currently, LAAC devices serve as a potential alternative to long-term anticoagulation with the benefit of decreased bleeding risk but with less protection against ischemic events. An individualized risk-benefit analysis with regard to stroke possibility, bleeding likelihood with long-term anticoagulation, the risks of an invasive procedure, and the risks associated with having a lifelong intracardiac device should be performed to guide careful patient selection for this operation.
Language	English
Publishing date	2019-01-15
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2156-3977
ISSN	2156-3977
DOI	10.19102/icrm.2019.100107
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Article ; Online: Bachmann bundle pacing.

Lustgarten, Daniel L / Habel, Nicole / Sánchez-Quintana, Damián / Winget, Joseph / Correa de Sa, Daniel / Lobel, Robert / Thompson, Nathaniel / Infeld, Margaret / Meyer, Markus

Heart rhythm

2024

Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2024.03.1786
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Article ; Online: Bachmann bundle potential during atrial lead placement: A case series.

Infeld, Margaret / Habel, Nicole / Wahlberg, Kramer / Meagher, Sean / Meyer, Markus / Lustgarten, Daniel

Heart rhythm

2021 Volume 19, Issue 3, Page(s) 490–494

MeSH term(s)	Atrial Fibrillation/surgery ; Cardiac Pacing, Artificial ; Electrocardiography ; Heart Atria/surgery ; Heart Conduction System ; Humans ; Membrane Potentials
Language	English
Publishing date	2021-11-12
Publishing country	United States
Document type	Case Reports ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2021.11.015
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