Association of Chronic Kidney Disease With Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction

Klein, David A.; Katz, Daniel H.; Beussink‐Nelson, Lauren; Sanchez, Cynthia; Strzelczyk, Theresa; Shah, Sanjiv J.

doi:10.1016/j.amjcard.2015.06.038

Cited by 34 publications

(24 citation statements)

References 33 publications

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“…HFpEF promotes renal dysfunction by 1) an elevated central venous pressure, which results from pulmonary hypertension and right ventricular dysfunction; 2) inability to raise cardiac output following arterial vasodilation because of chronotropic incompetence and fixed LV stroke volume 119 ; 3) systemic inflammation, endothelial dysfunction and low NO bioavailability, which reduces renal blood flow 55,120 and sodium excretion 44 . Renal dysfunction promotes HFpEF by worsening systemic inflammation, endothelial dysfunction and NO bioavailability partially because of renal-specific mediators such as high levels of fibroblast growth factor 23, phosphorus, parathyroid hormone or uremic toxins and low levels of vitamin D or erythropoietin 118 .…”

Section: Phenotypic Treatment Strategymentioning

confidence: 99%

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Shah¹,

et al. 2016

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Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for 50% of HF cases and its prevalence relative to HF with reduced EF (HFrEF) continues to rise. In contrast to HFrEF, large trials testing neurohumoral inhibition in HFpEF failed to reach a positive outcome. This failure was recently attributed to distinct systemic and myocardial signaling in HFpEF and to diversity of HFpEF phenotypes. In this review, a HFpEF treatment strategy is proposed which addresses HFpEF-specific signaling and phenotypic diversity. In HFpEF, extracardiac comorbidities such as metabolic risk, arterial hypertension and renal insufficiency drive left ventricular (LV) remodeling and dysfunction through systemic inflammation and coronary microvascular endothelial dysfunction. The latter affects LV diastolic dysfunction through macrophage infiltration resulting in interstitial fibrosis and through altered paracrine signaling to cardiomyocytes, which become hypertrophied and stiff because of low nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). Systemic inflammation also affects other organs such as lungs, skeletal muscle and kidneys leading respectively to pulmonary hypertension, muscle weakness and sodium retention. Individual steps of these signaling cascades can be targeted by specific interventions: metabolic risk by caloric restriction, systemic inflammation by statins, pulmonary hypertension by phosphodiesterase (PDE) 5 inhibitors, muscle weakness by exercise training, sodium retention by diuretics and monitoring devices, myocardial NO bioavailability by inorganic nitrate-nitrite, myocardial cGMP content by neprilysin or PDE 9 inhibition and myocardial fibrosis by spironolactone. Because of phenotypic diversity in HFpEF, personalized therapeutic strategies are proposed, which are configured in a matrix with HFpEF presentations in the abscissa and HFpEF predispositions in the ordinate.

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Section: Phenotypic Treatment Strategymentioning

confidence: 99%

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Shah¹,

et al. 2016

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“…Among cardiac mechanisms, ChI has been proposed as a pathophysiologic mechanism associated with poorer exercise capacity in a subgroup of patients with HFpEF . Along this same line, recent evidence has shown that ChI is frequently present (ranging from 20% to 75%) in HFpEF patients …”

Section: Discussionmentioning

confidence: 94%

“…Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is the predominant form of HF in western countries . Chronotropic incompetence (ChI), defined as the inability to increase heart rate during exercise adequately, is commonly present (ranging from 20 to 75%) in HFpEF patients . Furthermore, ChI has been proposed as a pathophysiologic mechanism associated with poorer outcomes and decreased functional capacity in a subgroup of patients with HFpEF …”

Section: Introductionmentioning

confidence: 99%

Beta‐blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve‐HR trial)

Palau

Seller²,

Domínguez

et al. 2020

Clinical Cardiology

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Background: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients. Hypothesis: We postulate beta-blockers may have deleterious effects in HFpEF andChI. This work aims to evaluate the short-term effect of beta-blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI.Methods: This is a prospective, crossover, randomized (1:1) and multicenter study.After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II-III, chronic treatment with beta-blockers, and ChI will be Abbreviations: ChI, chronotropic incompetence; CPET, cardiopulmonary exercise testing; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; NYHA, New York Heart Association; PeakVO2, peak exercise oxygen uptake; QoL, quality of life.Patricia Palau and Julia Seller contributed equally to this study.

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“…The prevalence of chronotropic incompetence reported among previous studies is widely variable, ranging from 20% to 75% . The criteria used to define chronotropic incompetence, as well as patient characteristics (age, disease severity, heart rhythm, and drug therapy), could explain these differences.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of chronotropic incompetence reported among previous studies is widely variable, ranging from 20% to 75%. [8][9][10][19][20][21] The criteria used to define chronotropic incompetence, as well as patient characteristics (age, disease severity, heart rhythm, and drug therapy), could explain these differences. In the present study, we postulate that the greater severity and the proportion of beta-blocker treatment (79.7%) of the patients may explain the higher prevalence of chronotropic incompetence here reported.…”

Section: Prevalence and Pathophysiology Of Chronotropic Incompetencementioning

confidence: 99%

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction

et al. 2018

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AimsThe mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF.Methods and resultsWe prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO2). The mean (standard deviation) peak VO2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta‐HR (HR at peak exercise − HR at rest), chronotropic index (CI) = (HR at peak exercise − resting HR)/[(220 − age) − resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise − HR at rest)/[119 + (HR at rest/2) − (age/2) − 5 − HR at rest]. In a bivariate setting, peak VO2 was positively and significantly correlated with Delta‐HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO2. We found a linear relationship between Delta‐HR and peak VO2 (β coefficient of 0.03; 95% confidence interval: 0.004–0.05; P = 0.030); conversely, the association among CIs and peak VO2 was exponentially shaped.ConclusionsIn patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity.

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Association of Chronic Kidney Disease With Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction

Cited by 34 publications

References 33 publications

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Beta‐blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve‐HR trial)

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction

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