Critical Care: Research Letter
Efficacy and Safety of Landiolol in Patients With Cardiogenic Shock
Giovanni Tavecchia, Guido Tavazzi, Giovanna Viola, et al
Chest Available online 25 March 2026
https://doi.org/10.1016/j.chest.2026.02.034
To the Editor:
Although compensatory tachycardia represents a normal physiologic response in patients with cardiogenic shock (CS), the presence of tachyarrhythmias (including disproportionate sinus tachycardia) can adversely impact cardiac output and be associated with further hemodynamic impairment. Nevertheless, there are no specific recommendations about the best approach to manage tachycardia in the critically ill cardiac patient. Landiolol, a highly cardioselective beta-blocker with a short half-life, has emerged as a potential tool for safe and titratable rate control in acute settings1, 2, 3 Two randomized clinical trials in patient populations with septic shock showed effective heart rate (HR) reduction without differences in safety endpoints between the 2 arms.4,5 The current evidence about the effects of landiolol in patients with CS remains limited.6, 7, 8
Methods
We conducted an observational analysis of patients treated with landiolol within a XXX registry between January 2023 and May 2025 at 2 XXX cardiac ICUs. The primary efficacy end point was HR reduction after landiolol initiation; safety endpoints included hemodynamic stability and adverse effects. Demographic and clinical data—including SCAI shock stage, cardiac rhythm, landiolol dose and duration, vasoactive therapy, and mechanical circulatory support—were collected. Stroke volume was estimated by transthoracic echocardiography as the product of left ventricular outflow tract (LVOT) cross-sectional area and LVOT velocity–time integral, according to standard recommendations.
The landiolol was up titrated by the lowest dose (1 μg/kg/min) up to the dose representing the HR target to the treating physician. The titration was performed in step of 1 μg/kg/min every 10-15 minutes as per protocol without changing other drugs. Hemodynamic parameters were assessed at baseline (T0) and at 2 (T1) and 24 hours (T24). Given the small sample size and non-normal distribution of several continuous variables, nonparametric tests were selected a priori. Continuous variables are reported as median (interquartile range [IQR]) or mean ± SD according to distribution. Changes over time were analyzed using the Friedman test, with post hoc Wilcoxon signed-rank tests and Bonferroni correction when appropriate. Categorical variables are presented as counts and percentages. Changes in SCAI stage were evaluated using McNemar test.
This study was approved by the local ethics committee of Milano Area 3 of the ASST Grande Ospedale Metropolitano Niguarda (Milan) and then by all local ethics committees of the hospitals participating in the registry. In accordance with the EU Regulation 536/2014, all competent patients provided written informed consent, whereas consent was waived for patients who were not competent on admission (clinical trial number: NCT04295252).
Results
Thirty-four patients were included (80% male; median age, 62 years [IQR, 56-75]). Indications for landiolol included atrial fibrillation (45%), sinus tachycardia (30%), refractory ventricular arrhythmias (15%), and atrial flutter (10%). CS causes were acute heart failure (37.1%), acute myocardial infarction-related CS (25.7%), and mixed shock (37.2%). Baseline SCAI stages were B (22.9%), C (54.3%), D (17.1%), and E (5.7%), with significant improvement at T24 (P < .001; Fig 1).
Thirty-two patients (94.4%) received landiolol during ongoing vasoactive therapy (adrenaline 42.7%, noradrenaline 37.1%, dobutamine 11.4%). Mechanical circulatory support was used in 34.4% (aortic balloon pump alone, 20%; veno-arterial extracorporeal membrane oxygenation ± unloading, 14.4%).
Landiolol was infused at a median dose of 10 μg/kg/min (IQR, 7.7-12) for 29.5 hours (IQR, 20-108). Initial HR was 129 beats/min (± 26); systolic and mean BP (SBP and MAP), respectively, 105 (± 11) mm Hg and 71 (± 12) mm Hg, with a pulse pressure of 49 (± 15) mm Hg. The initial lactates were 2.65 (± 1.5), Svo2, 61.3 (± 12)%; left ventricular ejection fraction, 27.1 (± 12)%; and echo-derived stroke volume, 33.8 (± 12) mL.
A significant HR reduction was observed from T0 to T1 (129 beats/min [IQR, 111-144] to 98 beats/min [IQR, 86-112], P < .001), with a further reduction at T24 (90 beats/min [IQR, 74-103]; P < .001). SBP and MAP remained unchanged at T1 but increased significantly at T24 (respectively, from 100 mm Hg [IQR, 90-115] to 115 mm Hg [IQR, 101-130]; P < .004, and 75 [IQR, 70.1-80.1] to 79.8 [74.7-84.9]); P < .002). Although left ventricular ejection fraction did not show any change throughout the time points, echo-derived SV increased significantly (Table 1). The vasopressor inotropic score significantly reduced from T1 to T24 (13.5 [0-40] vs 6.8 [0-30]; P < .01). Restoration of sinus rhythm was achieved in 40% of patients during landiolol infusion.
Table 1. Significant Hemodynamic Variations During the 3 Time Points
| Empty Cell | T0 | T2 | Median Difference [IQR] | T24 | Median Difference T0-T24 [IQR] | PValue |
|---|---|---|---|---|---|---|
| HR, beats/min | 129 [111 to 144] | 97 [86 to 112] | –31.5 [–49.5 to –8.25] | 89 [74 to 103] | –38 [–60 to –21.5] | < .001 |
| SBP, mm Hg | 105 [97 to 111] | 106 .5 (100.1 to 113.1)a | 0 [–8.75 to –10] | 115.8 (108 to 123)a | 5 [–4.25 to –22.75] | .03 |
| MAP, mm Hg | 71 [64.2 to 81.2] | 75.5 [71.5 to 81.7]a | 5 [13 to 8.75] | 79.1 [70.2 to 88.5]a | 4 [5 to 12.7] | .045 |
| SV, mL | 11.3 [8.5 to 15.4]a | 13.5 [9.1 to 16.9]a | 3.8 [4.3 to 3.9] | 16.9 [14.7 to 19.8]a | 5.3 [8.7 to 6.3 ] | .032 |
Data are presented as median [IQR] unless otherwise specified. Global P values derived from Friedman test. HR = heart rate; IQR = interquartile range; SBP = systolic BP; MAP = mean arterial pressure; SV = stroke volume; T0 = baseline; T2 = 2 hours; T24 = 24 hours.a
P < .05 vs T0 after Bonferroni correction for multiple comparisons.
Landiolol was used as first-line therapy in 33.3% of cases and following other antiarrhythmics in the remainder (33.3% after amiodarone, 11.1% after digoxin, and 11.1% after lidocaine). Transition to oral beta-blockers occurred in 45%, and to ivabradine in 7%. One patient (2.9%) developed bradycardia and hypotension requiring drug discontinuation 8 hours after the achievement of effective dose, without need for vasopressor escalation.
Discussion
Landiolol was associated with rapid and sustained heart rate control (median reduction, 30%) along with hemodynamic improvement in a real-world cardiac ICU population with cardiogenic and mixed shock. Notably, these effects were observed even in patients concurrently receiving catecholamines, without any apparent clinical interaction, despite both drug classes exerting effects on beta-adrenergic-receptors, representing a particularly significant finding. These results highlight how tachycardia, in response to acute reduction of cardiac output and BP in patients with shock, carries detrimental consequences that can be further worsened by the chronotropic effect of inotropic agents. A challenge is also the distinction between compensatory and disproportionate tachycardia.9 Although the former is meant to compensate the reduction in SV to maintain the cardiac output, the latter is defined once the detrimental effect of increased HR (diastolic filling time, increased metabolic demand, cardiac workload) overcomes the eventual beneficial effect of the CO increase. Evaluation of myocardial performance using echocardiography measuring the total isovolumic time in patients after cardiac surgery has highlighted the need for HR individualization according to patient’s phenotype and clinical conditions.10 Landiolol has been evaluated in a large observational multicenter study including 450 adult patients with supraventricular arrhythmias, of whom approximately 15% had underlying cardiac conditions such as perimyocardial infarction or acute decompensated heart failure.11 In addition, a single-center study focusing on patients with heart failure has been reported.12 Both studies demonstrated effective HR reduction accompanied by an increase in BP and a low incidence of adverse events (17% and 6%, respectively), none of which required clinical intervention; in the multicenter study, adverse events were not clearly attributable to landiolol. More recently, a comparative study in nonsurgical critically ill patients admitted for hemodynamic instability related to tachyarrhythmias (10 patients treated with landiolol vs 41 receiving standards of care) confirmed the effectiveness of landiolol in controlling HR without a detrimental impact on BP.13 Our study adds to the existing literature by describing landiolol use across a broad spectrum of cardiogenic shock severity, as defined by SCAI stages, in a population with a high prevalence of concomitant inotropic support and mechanical circulatory support.
This study has several limitations. The population was heterogeneous with respect to shock cause, arrhythmia type, and severity, which may limit generalizability. The observational design and absence of a comparator group preclude causal inference, and selection bias related to physician-driven treatment decisions cannot be excluded. Time-varying co-interventions, including vasoactive drug titration and adjustments in mechanical circulatory support, may have contributed to the observed hemodynamic changes and cannot be fully disentangled from the effects of landiolol. However, all the changes were minimizing the support (VIS reduction) once the hemodynamic had improved. Finally, hemodynamic improvements observed at 24 hours may reflect the natural evolution of shock or concomitant therapies rather than a direct effect of landiolol.
Because this report works as hypothesis generation, if confirmed in larger, prospective controlled clinical trials, with rigorous design, these results may position landiolol as a valuable therapeutic option that is short acting, easily titratable, well tolerated, and safe to mitigate the adverse effects of inappropriate tachycardia in this critically ill cardiac population. Although the observed improvement in CS severity by SCAI stage at T24 of landiolol infusion is a promising finding, it cannot be attributed solely to landiolol; the associated HR reduction likely contributed meaningfully to hemodynamic stabilization, potentially minimizing the risks associated with excessive sympathetic drive.
In conclusion, in a cohort of selected patients received advanced therapies because of cardiogenic or mixed shock, the use of landiolol was associated with a reduction of HR with an improvement in hemodynamic parameters during the 24-hour treatment period.
