Algorithm to choose optimal β-Blocker in patients with Heart Failure

Introduction

β-blockers are effective in the treatment of heart failure (HF) and have shown to improve clinical outcomes. However, HF patients with respiratory comorbidities remain undertreated with β-blockers despite recent consensus that HF treatment with β-blockers should be considered even in the presence of respiratory comorbidities, with the sole exception of true severe asthma.

Pharmacologically, the different β-blockers that have been clinically shown to be effective in HF, often differ in their selectivity of the β-receptor subtypes. For instance, carvedilol has high affinity to bind with both β1 and β2 receptors (β1β2 blocker); in contrast, bisoprolol has higher β1 selectivity.

Notably, the β1 receptors are predominantly located in cardiac tissues, while the β2 receptors are predominantly expressed in the respiratory tissues. An important clinical significance of this differential expression is that, while β1 blockade, via reduced sympathetic activity, provides a therapeutic effect in heart failure; conversely, the β2 stimulation, via bronchodilation, provides the therapeutic effect in airway/respiratory diseases.

This distinction among β-blockers based on their selectivity to bind with β1 or β2 receptor might not be very important in all patients with HF. However, in the subset of HF patients with compromised respiratory physiology, such as those with chronic obstructive pulmonary disease (COPD), or restrictive lung disease, the different selectivity of β-blockers may show clinically meaningful differences. However, the current clinical guidelines do not address this aspect satisfactorily. The present study, a narrative review by Sinagra et al.,1 attempted to address this knowledge gap.

Aims

This review aimed to evaluate the differences between β1-selective and β1-β2 blockers in the context of HF, and propose an algorithm for optimal β-blocker selection in patients with HF based on the β-selectivity of different β-blockers.

β Selectivity and Heart-Lung Interactions

HF can worsen the respiratory function by restricting the lung function and diffusion capacity (DLCO), and by increasing the inefficient ventilation and the slope of ventilation (VE/VCO2). These negative effects of HF on the respiratory system seem to be compensated by the body via β2 receptors. Therefore, using a β1β2-blocker, but not a β1-blocker, in HF might worsen the DLCO and VE/VCO2 (Figure 1).

Figure 1: β1 vs β1β2 Blockade in Heart Failure

Proposed Algorithm

Based on the anatomical location and functioning of β1 and β2 receptors, Sinagra et al.1 proposed the following algorithm (Figure 2). As can be noted from the algorithm, β1-selective blockers, such as bisoprolol were preferred in the majority of the cases, including in those with low DLCO (<80% predicted), and among those with respiratory comorbidities even with DLCO >80%. In the case of those with a normal DLCO and without respiratory comorbidities, the VE/VCO2 could influence the selection of β-blocker (a preference to β1-selective blocker when VE/VCO2 <34).

Figure 2: Algorithm for Choosing β-blocker in HF

Conclusions

The suggested algorithm may be a useful tool to optimize β-blocker treatment in patients with HF. β1-selective blockers may be preferred in HF accompanied with low DLCO, and preserved DLCO but with concomitant severe COPD. However, the suggested algorithm has not been clinically tested and does not consider the other clinical parameters that might also influence the choice of β-blocker.

References:
Sinagra G, Corrà U, Contini M, et al. Choosing among β-blockers in heart failure patients according to β-receptors’ location and functions in the cardiopulmonary system. Pharmacological Research.

CODE: IN-CONCO-00023