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, Patricia; Seller, Julia; Domínguez, Eloy; Gómez, Inés; Ramón, José; Sastre, Clara; Espriella, Rafael de la; Santas, Enrique; Miñana, Gema; Chorro, Francisco J.; González-Juanatey, José Ramón; Núñez, Julio

doi:10.1002/clc.23345

Cited by 19 publications

(14 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with above findings on neurohumoral activation, betablockers have not been found beneficial in clinical studies in HFpEF patients, and maybe even harmful by worsening impaired chronotropic responses in some patients (121). In fact, withdrawal of pre-existing betablocker therapy in HFpEF patients is currently investigated as a therapeutic approach (122).…”

Section: Neurohumoral Activationmentioning

confidence: 89%

Left ventricular dysfunction in heart failure with preserved ejection fraction—molecular mechanisms and impact on right ventricular function

Heinzel¹,

Hegemann²,

Hohendanner³

et al. 2020

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

The current classification of heart failure (HF) based on left ventricular (LV) ejection fraction (EF) identifies a large group of patients with preserved ejection fraction (HFpEF) with significant morbidity and mortality but without prognostic benefit from current HF therapy. Co-morbidities and conditions such as arterial hypertension, diabetes mellitus, chronic kidney disease, adiposity and aging shape the clinical phenotype and contribute to mortality. LV diastolic dysfunction and LV structural remodeling are hallmarks of HFpEF, and are linked to remodeling of the cardiomyocyte and extracellular matrix.Pulmonary hypertension (PH) and right ventricular dysfunction (RVD) are particularly common in HFpEF, and mortality is up to 10-fold higher in HFpEF patients with vs. without RV dysfunction. Here, we review alterations in cardiomyocyte function (i.e., ion homeostasis, sarcomere function and cellular metabolism) associated with diastolic dysfunction and summarize the main underlying cellular pathways. The contribution and interaction of systemic and regional upstream signaling such as chronic inflammation, neurohumoral activation, and NO-cGMP-related pathways are outlined in detail, and their diagnostic and therapeutic potential is discussed in the context of preclinical and clinical studies. In addition, we summarize prevalence and pathomechanisms of RV dysfunction in the context of HFpEF and discuss mechanisms connecting LV and RV dysfunction in HFpEF. Dissecting the molecular mechanisms of LV and RV dysfunction in HFpEF may provide a basis for an improved classification of HFpEF and for therapeutic approaches tailored to the molecular phenotype.

show abstract

Section: Neurohumoral Activationmentioning

confidence: 89%

Left ventricular dysfunction in heart failure with preserved ejection fraction—molecular mechanisms and impact on right ventricular function

Heinzel¹,

Hegemann²,

Hohendanner³

et al. 2020

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

show abstract

“…Recent studies have indicated unfavorable hemodynamic effects of pharmacological lowering of HR within a subgroup of patients with normal ejection fraction 64 – 66 . Whereas increasing HR in a pacemaker study of patients with preserved ejection fraction within a physiological range has shown improvement in patients with HFpEF 63 , 64 .…”

Section: Discussionmentioning

confidence: 99%

Investigating the effects of beta-blockers on circadian heart rhythm using heart rate variability in ischemic heart disease with preserved ejection fraction

Saleem

Khandoker

Alkhodari

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Heart failure is characterized by sympathetic activation and parasympathetic withdrawal leading to an abnormal autonomic modulation. Beta-blockers (BB) inhibit overstimulation of the sympathetic system and are indicated in heart failure patients with reduced ejection fraction. However, the effect of beta-blocker therapy on heart failure with preserved ejection fraction (HFpEF) is unclear. ECGs of 73 patients with HFpEF > 55% were recruited. There were 56 patients in the BB group and 17 patients in the without BB (NBB) group. The HRV analysis was performed for the 24-h period using a window size of 1,4 and 8-h. HRV measures between day and night for both the groups were also compared. Percentage change in the BB group relative to the NBB group was used as a measure of difference. RMSSD (13.27%), pNN50 (2.44%), HF power (44.25%) and LF power (13.53%) showed an increase in the BB group relative to the NBB group during the day and were statistically significant between the two groups for periods associated with high cardiac risk during the morning hours. LF:HF ratio showed a decrease of 3.59% during the day. The relative increase in vagal modulated RMSSD, pNN50 and HF power with a decrease in LF:HF ratio show an improvement in the parasympathetic tone and an overall decreased risk of a cardiac event especially during the morning hours that is characterized by a sympathetic surge.

show abstract

“…The relationship between beta-blockers, chronotropic response, and EC is currently under investigation, and there are many ambiguities regarding this issue [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers: Real-Life Observation of Consecutive Patients

et al. 2021

View full text Add to dashboard Cite

Background: Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear. Methods: We analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing to assess EC. Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. Results: Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), 64% with heart failure, chronotropic incompetence was present in 80.7%. EC assessed as peak oxygen uptake was lower in the group with chronotropic incompetence, 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = −0.17, p < 0.001) and presence of heart failure (β = −3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI accounted for more than one-third of the variance in EC explained by the model (adjusted R2 = 59.8%). Conclusions: In patients taking beta-blockers, presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

show abstract

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)

Cited by 19 publications

References 40 publications

Left ventricular dysfunction in heart failure with preserved ejection fraction—molecular mechanisms and impact on right ventricular function

Left ventricular dysfunction in heart failure with preserved ejection fraction—molecular mechanisms and impact on right ventricular function

Investigating the effects of beta-blockers on circadian heart rhythm using heart rate variability in ischemic heart disease with preserved ejection fraction

Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers: Real-Life Observation of Consecutive Patients

Contact Info

Product

Resources

About