Abstract 812: Mechanisms of Sinus Node Dysfunction and Chronotropic Incompetence in Rats with Heart Failure and Preserved Ejection Fraction

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Thassio Mesquita ◽  
Jae H Cho ◽  
Rui Zhang ◽  
Joshua I Goldhaber ◽  
Eduardo Marbán ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Sinus Node ◽  
Sinus Node Dysfunction ◽  
Preserved Ejection Fraction ◽  
Chronotropic Incompetence

scholarly journals Mechanisms of Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 13 (3) ◽  
Author(s):  
Satyam Sarma ◽  
Douglas Stoller ◽  
Joseph Hendrix ◽  
Erin Howden ◽  
Justin Lawley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Chronotropic Incompetence

Abstract 17050: Association of Kidney Dysfunction with Chronotropic Incompetence in Heart Failure with Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
David A Klein ◽  
Daniel H Katz ◽  
Lauren Beussink-Nelson ◽  
Theresa A Strzelczyk ◽  
Sanjiv J Shah
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Regression Models ◽  
Beta Blockers ◽  
Cardiopulmonary Exercise Testing ◽  
Systolic Pressure ◽  
Maximal Heart Rate ◽  
Preserved Ejection Fraction ◽  
Chronotropic Incompetence ◽  
Chronotropic Response

Introduction: Chronotropic incompetence (CI) is an important pathophysiologic factor underlying reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF), but clinical factors associated with CI in HFpEF are unknown. Based on anecdotal clinical experience, we hypothesized that coronary artery disease (CAD) and chronic kidney disease (CKD) are associated with CI in HFpEF. Methods: We studied 157 consecutive HFpEF patients undergoing cardiopulmonary exercise testing, and defined CI as maximal heart rate (HR) < 80% of estimated HR reserve (< 65% if using beta-blockers). Participants who achieved inadequate exercise effort (respiratory exchange ratio [RER] ≤ 1.05) were excluded. Unadjusted and multivariable-adjusted regression models were used to determine correlates of CI. Results were re-assessed using alternative formulations of chronotropic response. Results: Of 157 participants, 73% were women, 64% used beta-blockers, 32% had CKD, and 40% had CAD. RER > 1.05 was achieved by 108 (69%) participants, including 79/108 (76%) with CI. Lower estimated GFR, higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure (but not CAD) were each associated with CI. A 1-SD decrease in GFR was independently associated with CI (adjusted odds ratio = 2.4, 95% confidence interval = [1.3, 4.6]) after adjustment for smoking status, log BNP, and beta blocker usage. Linear regression models demonstrated that GFR was independently and linearly associated with %HR reserve (β=0.31, SE=0.10; P=0.002; Figure). Findings were unchanged after re-calculation of %HR reserve and CI based on alternative formulations used in the literature. Conclusions: CI is common and strongly associated with GFR in HFpEF. Our results indicate that kidney function may mark or contribute to the development of CI in HFpEF. HFpEF patients with CKD may need to be screened for CI prior to starting medications (e.g., beta blockers) that could exacerbate CI.

Chronotropic Incompetence Predicts Distance Walked in Six-Minute Walk Test in Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 26 (11) ◽  
pp. 1024-1025
Author(s):  
Patricia Palau ◽  
Eloy Domínguez ◽  
Julia Seller ◽  
Clara Sastre ◽  
Antoni Bayés-Genís ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Walk Test ◽  
Chronotropic Incompetence ◽  
Six Minute Walk Test ◽  
Minute Walk

scholarly journals Impaired Heart Rate Recovery and Chronotropic Incompetence in Patients With Heart Failure With Preserved Ejection Fraction

2010 ◽  
Vol 3 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Thanh Trung Phan ◽  
Ganesh Nallur Shivu ◽  
Khalid Abozguia ◽  
Chris Davies ◽  
Mohammad Nassimizadeh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Heart Rate Recovery ◽  
Preserved Ejection Fraction ◽  
Chronotropic Incompetence ◽  
Patients With Heart Failure

Echocardiographic Predictors of Chronotropic Incompetence to Exercise in Patients with Heart Failure with Preserved Ejection Fraction

PRILOZI ◽  
2014 ◽  
Vol 35 (2) ◽  
pp. 137-145
Author(s):  
Zharko Hristovski ◽  
Daniela Projevska-Donegati ◽  
Ljubica Georgievska-Ismail
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction ◽  
Chronotropic Incompetence ◽  
Average Ratio ◽  
Significant Difference ◽  
Patients With Heart Failure ◽  
Echocardiographic Parameters

Abstract Objective: Exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) is most often attributed to diastolic dysfunction (DD); however, chronotropic incompetence (CI) could also play an important role. We intended to examine whether there are predictive echocardiographic parameters of DD for impaired chronotropic response to exercise. Methods and Results: Patients (n = 143) with unexplained dyspnea and/or exercise intolerance who fulfilled clinical and echocardiographic criteria of HFpEF presence underwent a symptom-limited exercise test using a treadmill (ETT) according to the Bruce protocol. CI was defined as an achieved heart rate reserve (HRR) of ≤ 80%. Comparison of the groups with (n = 98) and without CI (n = 45) did not show any statistically significant difference regarding demographic and clinical character-ristics except for use of beta blockers (BB) that were more frequently present (p = 0.012) in patients with CI in comparison with those without. Patients with CI had a higher mean E-wave velocity, E/A ratio, increased E/E‵ septal, lateral as well as average ratio and abnormal IVRT/TE-e‵ index all consistent with elevated LV filling pressures. E/E‵ average ratio > 15 was statistically insignificantly more frequently present in patients with CI. In addition, by multivariate stepwise regression analysis value of E‵ septal (β = 3.697, 95%CI 0.921–6.473, p = 0.009) along with use of BB, current smoking and basal heart rate appeared as statistically significant independent predictors of lower HRR %. Conclusion: Patients with HFpEF frequently have chronotropic incompetence to graded exercise which may partly be predicted with echocardiographic parameters that are consistent with elevated LV filling pressures.

Mechanisms of Sinoatrial Node Dysfunction in Heart Failure with Preserved Ejection Fraction

Circulation ◽  
2021 ◽  
Author(s):  
Thassio Mesquita ◽  
Rui Zhang ◽  
Jae Hyung Cho ◽  
Rui Zhang ◽  
Yen-Nien Lin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Single Cell ◽  
Sinoatrial Node ◽  
Ex Vivo ◽  
Normal Diet ◽  
Preserved Ejection Fraction ◽  
Chronotropic Incompetence ◽  
Chronotropic Response

Background: The ability to increase heart rate (HR) during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiologic HR response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure (HF) and preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown. Methods: Dahl salt-sensitive rats fed with a high-salt diet and C57Bl6 mice fed with high fat and an inhibitor of constitutive nitric oxide synthase (L-NAME, 2-hit) were used as models of HFpEF. Myocardial infarction was created to induce HF with reduced ejection fraction (HFrEF). Rats and mice fed with a normal diet or having a sham surgery served as respective controls. A comprehensive characterization of SAN function and chronotropic response was conducted by in vivo, ex vivo, and single-cell electrophysiological studies. RNA sequencing of SAN was performed to identify transcriptomic changes. Computational modeling of biophysically-detailed human HFpEF SAN was created. Results: Rats with phenotypically-verified HFpEF exhibited limited chronotropic response associated with intrinsic SAN dysfunction, including impaired β-adrenergic responsiveness and an alternating leading pacemaker within the SAN. Prolonged SAN recovery time and reduced SAN sensitivity to isoproterenol were confirmed in the 2-hit mouse model. Adenosine challenge unmasked conduction blocks within the SAN, which were associated with structural remodeling. Chronotropic incompetence and SAN dysfunction were also found in HFrEF rats. Single-cell studies and transcriptomic profiling revealed HFpEF-related alterations in both the "membrane clock" (ion channels) and the "Ca 2+ clock" (spontaneous Ca 2+ release events). The physiological impairments were reproduced in silico by empirically-constrained quantitative modeling of human SAN function. Conclusions: Thus, chronotropic incompetence and SAN dysfunction were seen in both models of HF. We identified that intrinsic abnormalities of SAN structure and function underlie the chronotropic response in HFpEF.

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