Chronic mitral regurgitation is the most common valvular abnormality worldwide, it occurs in 10% of the general population and its prevalence increases with age. When left untreated, it can lead to left ventricular dysfunction and cause disabling symptoms (e.g., fatigue and dyspnea), life-threatening complications (e.g., ventricular dilation, congestive heart failure) and death. Surgical correction of chronic mitral regurgitation before irreversible changes happen can be curative. Open surgical valve repair or replacement are accomplished through cardiopulmonary bypass and cardioplegic arrest. Myocardial protection is essential to guarantee an uneventful perioperative course since a not-well protected heart may lead to postoperative low-cardiac output syndrome. This occurs in 30% of high-risk patients who undergo elective cardiac surgery and is associated with 20% mortality. Cardioplegia preserves the heart during ischemic arrest by reducing its metabolic demand. The most effective cardioplegia for protection in adult cardiac surgery remains unknown and improving the protection of the heart during the ischemic arrest may potentially improve patients' postoperative outcomes. Pharmacological adjuvants to the cardioplegic solutions have been tested to mitigate the ischaemic-reperfusion injury following cardiac surgery. Ultra-short acting beta-blockers (e.g., esmolol, landiolol) decrease intraoperative myocardial metabolic demand and suppress the sympathetic response to surgical stimuli while exhibiting limited adverse effects. Few studies with limited sample size investigated the role of ultra-short acting beta-blockers in reducing perioperative ischaemia and arrhythmia after cardiac surgery. When ultra-short acting beta-blockers were administered before aortic cross-clamping and as cardioplegia adjuvant we observed a trend towards a reduction in postoperative low-cardiac output syndrome (13/98 vs 6/102; p=0.08) and in the rate of hospital re-admission at one year (26/95 v 16/96, p=0.08) with an increase in the number of patients with ejection fraction \>60% at hospital discharge (4/95 vs 11/92, p=0.06) (Zangrillo 2021). However, despite a growing body of literature exploring the role of ultra-short acting beta-blockers in enhancing myocardial protection during on-pump cardiac surgery, further high-quality evidence is needed before this practice can be established as standard routine care. Hence, we designed a randomized, placebo-controlled trial involving 1500 patients undergoing open mitral valve surgery to assess the effect of administering landiolol as cardioplegia adjuvant to reduce the occurrence of postoperative low-cardiac output syndrome. Successful results would have a significant impact on short and long-term complications.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
1,500
Ospedale Cesare Arrigo
Alessandria, Piedmont, Italy
RECRUITINGA. O. Ordine Mauriziano di Torino
Torino, TO, Italy
RECRUITINGAOU di Alessandria
Alessandria, Italy
RECRUITINGAzienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"
Catania, Italy
RECRUITINGAOU Careggi
Florence, Italy
RECRUITINGAzienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
Foggia, Italy
RECRUITINGIRCCS San Martino di Genova
Genova, Italy
RECRUITINGOspedale San Raffaele
Milan, Italy
RECRUITINGASST Grande Ospedale Metropolitano Niguarda
Milan, Italy
RECRUITINGAOU Policlinico Paolo Giaccone
Palermo, Italy
RECRUITING...and 3 more locations
Reduction of the occurrence of postoperative low-cardiac output syndrome (LCOS)
The primary outcome will be the reduction of the occurrence of postoperative low-cardiac output syndrome, defined following Cholley et al. 2017 JAMA as the presence of at least one of the following: 1. need of prolonged catecholamine infusion (persisting beyond 48 hours after the initiation of the study drug); 2. need of circulatory mechanical assist devices in the postoperative period (if an intra-aortic balloon pump was inserted preventively, the criteria will be met if patients are not weaned from the balloon within 96 hours); 3. need for renal replacement therapy at any time during the intensive care unit stay.
Time frame: Until ICU discharge, an average of 4 days
Patients requiring prolonged (>48 h) catecholamine infusion
Time frame: Until ICU discharge, an average of 4 days
Patients with increased postoperative cardiac biomarkers (Troponin I or T)
Time frame: Up to 48 hours.
Patients with a reduction in left ventricular ejection fraction
Time frame: Until hospital discharge, an average of 10 days
Number of patients readmitted to hospital for cardiac reasons
Time frame: 1 year
EQ-5D-5L questionnaire
Time frame: 1 year
Death
Time frame: 1 year
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