Personalised perioperative dosing of ivabradine in noncardiac surgery: a single-centre, randomised, placebo-controlled, double-blind feasibility pilot trial.

BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.

Myocardial injury after major noncardiac surgery: A secondary analysis of a randomized controlled trial.

BACKGROUND: Myocardial injury after noncardiac surgery frequently occurs and may influence survival. The aims of this study were to examine the association between myocardial injury after noncardiac surgery and patient and procedural factors as well as its impact on postoperative clinical outcome. METHODS: A retrospective analysis was conducted from data collected in adults enrolled in a randomized trial in elective major open abdominal surgery. Preoperative patient characteristics, intraoperative hemodynamic changes, and postoperative adverse events were analyzed, and Kaplan-Meier curves were built for postoperative survival probability. After adjustment for baseline patient and procedural characteristics, the effect of myocardial injury after noncardiac surgery on postoperative outcomes was analyzed in a propensity score matched cohort. RESULTS: Among 394 patients, myocardial injury after noncardiac surgery was reported in 109 (27.7%) and was associated with a higher cardiovascular risk profile, prolonged surgery (333 ± 111 min vs 295 ± 134 min, P = .010), greater need for transfusions (41.3% vs 19.3%, P < .001), higher incidence of major adverse cardiac events (22.9% vs 6.7%, P < .001), pulmonary complications (31.2% vs 17.9%, P = .004) , acute kidney injury (30.3% vs 18.2%, P = .009), and systemic inflammatory syndrome (28.4% vs 13.0%, P < .001). After propensity score matching, the operative time and the need for blood transfusion remained higher among myocardial injury after noncardiac surgery patients who experienced more frequent major adverse cardiac events and acute kidney injury. In both the entire and matched cohorts, survival up to 30 months after surgery was determined mainly by the presence of cancer. CONCLUSION: The burden of cardiovascular disease and operative stress surgery is predictive of myocardial injury after noncardiac surgery and, in turn, with a higher incidence of cardiac adverse events, whereas the presence of cancer is associated with poor survival in patients undergoing major open abdominal surgery. Further studies are needed to determine whether myocardial injury after noncardiac surgery can be prevented by better control of the patient's cardiovascular condition and implementation of less invasive of surgical procedures.

Goal-directed hemodynamic therapy versus restrictive normovolemic therapy in major open abdominal surgery: A randomized controlled trial.

BACKGROUND: The aim of this study was to compare the occurrence of postoperative complications in patients undergoing elective open abdominal surgery and receiving intraoperative goal-directed hemodynamic therapy or restrictive normovolemic therapy. METHODS: A total of 401 patients were randomized in the goal-directed hemodynamic therapy or restrictive normovolemic therapy groups. A cardiac output monitor was used in all goal-directed hemodynamic therapy patients and was left at the discretion of anesthetists in charge of patients in the restrictive normovolemic therapy group. The primary outcome was a composite morbidity endpoint (30-day mortality and complications grade 2-4 according to Dindo-Clavien classification). Secondary outcomes were the hospital duration of stay, the incidence of pulmonary, cardiovascular, and renal complications up to 30 days after surgery, and midterm survival. RESULTS: Intraoperatively, the goal-directed hemodynamic therapy group received higher intravenous fluid volumes (mean of 10.8 mL/kg/h and standard deviation of 4.0) compared with the restrictive normovolemic therapy group (mean of 7.2 mL/kg/h and standard deviation of 2.0; P < .001). On the first postoperative day, similar fluid volumes were infused in the 2 groups. The primary outcome occurred in 57.7% of goal-directed hemodynamic therapy and 53.0% of restrictive normovolemic therapy (relative risk, 1.09 [95% confidence interval, 0.91-1.30]), and there was no significant difference between groups for any secondary outcomes. CONCLUSION: Among patients undergoing major open abdominal surgery, the goal-directed hemodynamic therapy and the restrictive normovolemic therapy were associated with similar incidence of moderate-to-severe postoperative complications and hospital resource use.

Improved Exercise Tolerance, Oxygen Delivery, and Oxygen Utilization After Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) represents an effective therapeutic procedure, particularly in patients with severe aortic stenosis. We hypothesized that the decreased afterload induced by TAVI would improve exercise capacity by enhancing oxygen uptake in working muscles. METHODS: A standardized exercise test was performed in patients with severe aortic stenosis the day before TAVI and within 5 days thereafter. The main study endpoint was the workload achieved during a 5-minute standardized exercise test. Using electrical cardiometry and near-infrared spectroscopy, we explored and compared the changes in cardiac index (CI), as well as muscular and cerebral tissue oximetry, during the 2 exercise tests. RESULTS: Thirty patients completed the study protocol. Compared with the pre-TAVI period, patients achieved a higher median workload after TAVI (316 Joules [interquartile range {IQR}: 169-494] vs 190 Joules [IQR: 131-301], P = 0.002). Baseline CI increased from 2.5 l/min per m2 (IQR: 2.1-2.9) to 2.9 l/min per m2 (IQR: 2.5-3.2; P = 0.009), whereas CI at the end of the exercise test increased from 4.5 l/min per m2 (IQR: 3.4-5.3) to 4.7 l/min per m2 (3.4-6.4; P = 0.019). At the end of the exercise test, cerebral tissue oximetry increased from 70% (IQR: 65-72) to 74% (IQR: 66-78), and muscle tissue oximetry increased from 62% (IQR: 58-65) to 71% (65-74; P = 0.046 and P < 0.001, respectively). CONCLUSIONS: Early improvement of exercise capacity after TAVI is associated with increased CI and better oxygen utilization in the brain and skeletal muscles.

CONTEXTE: Le remplacement valvulaire aortique par cathéter (TAVI) représente une procédure thérapeutique efficace, en particulier chez les patients présentant une sténose aortique sévère. Nous avons émis l'hypothèse que la diminution de la postcharge induite par le TAVI améliorerait la capacité à l'effort en favorisant la consommation d'oxygène des muscles travaillant. MÉTHODES: Un test d'effort standardisé a été réalisé chez des patients souffrant de sténose aortique sévère la veille de l'intervention TAVI et dans les 5 jours qui ont suivi. Le principal critère d'évaluation de l'étude était la charge de travail atteinte lors d'un test d'effort standardisé de 5 minutes. En utilisant la cardiométrie électrique et la spectroscopie proche infrarouge, nous avons exploré et comparé les changements de l'index cardiaque (IC), ainsi que l'oxymétrie des tissus musculaires et cérébraux, pendant les 2 tests d'effort. RÉSULTATS: Trente patients ont terminé le protocole d'étude. Par rapport à la période pré-TAVI, les patients ont atteint une charge de travail médiane plus élevée après le TAVI (316 Joules [intervalle interquartile (IIQ) : 169-494] contre 190 Joules [IIQ : 131-301], p = 0.002). L'IC de base est passé de 2,5 l/min par m2 (IIQ : 2,1-2,9) à 2,9 l/min par m2 (IIQ : 2,5-3,2 ; p = 0.009), tandis que l'IC à la fin du test d'effort est passé de 4,5 l/min par m2 (IIQ : 3.4-5.3) à 4,7 l/min par m2 (3,4-6,4 ; p = 0,019). À la fin du test d'effort, l'oxymétrie du tissu cérébral est passée de 70 % (IIQ : 65-72) à 74 % (IIQ : 66-78), et l'oxymétrie du tissu musculaire est passée de 62 % (IIQ : 58-65) à 71 % (65-74; p = 0,046 et p < 0,001, respectivement). CONCLUSIONS: L'amélioration précoce de la capacité d'exercice après le TAVI est associée à un IC accru et à une meilleure utilisation de l'oxygène au niveau du cerveau et des muscles squelettiques.