The MICRA-HYBRID trial is a prospective, multicenter, randomized controlled study comparing multivessel hybrid coronary revascularization (HCR) as minimally invasive arterial bypass grafting to left-sided coronary targets (LAD and LCx) plus PCI of the RCA versus conventional off-pump coronary artery bypass grafting (OPCAB) via median sternotomy in patients with three-vessel coronary artery disease. The primary goal is to evaluate whether multivessel-HCR provides superior 30-day "textbook" clinical outcomes (mortality, MI, stroke, re-exploration for bleeding, and other complications) while improving perioperative recovery and long-term cardiovascular outcomes.

Coronary artery disease remains the leading cause of cardiovascular mortality worldwide. For complex, multivessel disease, surgical revascularization via CABG or OPCAB remains the guideline-recommended standard due to superior long-term outcomes compared with PCI alone. However, traditional sternotomy CABG/OPCAB is associated with significant surgical trauma, prolonged recovery, and elevated perioperative morbidity.

Minimally invasive coronary surgery (MICS) with off-pump arterial grafting through a small thoracotomy has shown favorable short-term recovery and lower morbidity in both single and multivessel disease cases. Traditionally, MICS has been limited to grafting the left anterior descending artery (LAD), with other coronary lesions treated by PCI, known as hybrid coronary revascularization (HCR). While most studies have focused on single-vessel HCR (typically LAD), the potential long-term benefits of including the circumflex (Cx) artery in a multivessel-HCR strategy remain unexplored. Given that three-vessel CAD is the most common indication for CABG, evaluating a multivessel-HCR approach (LAD + Cx via MICS, RCA via PCI) is essential.

The MICRA-HYBRID trial will randomize 250 patients with three-vessel coronary disease eligible for complete revascularization to either multivessel-HCR or conventional total-arterial OPCAB (median sternotomy, anaortic, off-pump). The primary efficacy endpoint is a composite "Textbook Outcome" at 30 days, defined by absence of death, MI, stroke, re-exploration for bleeding, and other major complications. Secondary endpoints include individual components of the Textbook Outcome, perioperative recovery parameters (ICU/hospital length of stay, ventilator time, transfusion requirement), health-related quality of life (EQ-5D), pulmonary recovery metrics, angina class (CCS), and long-term outcomes including MACCE and target-vessel revascularization up to five years.

Inclusion Criteria:

• Patients with three-vessel disease (either angiographic stenoses >70% or a fractional flow reserve value ≤0.80)
• Left main diameter stenosis ≥50% or a left main intravascular ultrasound minimal luminal area of ≤4.5 mm2 or fractional flow reserve value ≤0.80 combined with significant CAD of the right coronary artery

Exclusion Criteria:

A potential participant who meets any of the following criteria will be excluded from participation in this study:

• Age < 18 or > 85 years
• Chronic total occlusion of the RCA
• In-stent RCA restenosis
• RCA stenosis with high-risk clinical features requiring urgent PCI or surgical revasculari-zation.
• Reverse hybrid coronary revascularization, defined as PCI-RCA followed by surgical re-vascularization.
• Acute cardiac ischemia necessitating immediate intervention.
• EF < 30 %
• eGFR < 30 ml/min
• Indication for concomitant cardiac surgery (e.g. valve or arrhythmia surgery) or non-cardiac surgery
• Previous thoracic or cardiac surgery, mediastinal irradiation, significant trauma to the chest
• Preoperative severe end-organ dysfunction (dialysis, liver failure, respiratory failure) or cancer.
• Hemodynamically significant left subclavian stenosis
• Severe chest wall deformities
• History of pericarditis
• Body mass index > 40 Kg/m2.

IPD could be made available upon request to the Principal Investigator after the study's completion.