Evolut™ EXPAND TAVR II Pivotal Trial

Multi-center, international, prospective, randomized study. Subjects will be randomized to either transcatheter aortic valve replacement (TAVR) with the Evolut PRO+ TAVR System, or Evolut FX System, and guideline-directed management (GDMT) or GDMT alone.

Key Inclusion Criteria:

o Moderate AS, defined as follows by transthoracic echo (TTE) as assessed by the ECL:

• AVA >1.0 cm² and <1.5cm²; or
• AVA ≤ 1.0 cm² with AVAI > 0.6cm²/m² if BMI < 30 kg/m²: or
• AVA ≤ 1.0 cm² with AVAI > 0.5cm²/m² if BMI ≥ 30 kg/m²:

and

• Max aortic velocity ≥ 3.0 m/sec. and < 4.0 m/sec. or
• Mean aortic gradient ≥ 20mmHg and < 40.0 mmHg

Any of the following at-risk features:

• Symptoms of AS, defined as:
• NYHA ≥ Class II, or
• Reduced functional capacity, defined as

• 6MWT < 300 meters, or
• < 85% of age-sex predicted METs on exercise tolerance testing (ETT)
• Documented heart failure event or hospitalization for heart failure within 1 calendar year prior to consent
• NT-proBNP ≥ 600 pg/ml (or BNP ≥ 80 pg/ml), or
• Persistent AF or Paroxysmal AF episode within 6 months prior to consent, or
• Elevated aortic valve calcium score (>1200 AU for females and > 2000 AU for males) as assessed by the MDCT core lab, or
• Any of the following by the qualifying TTE as assessed by the ECL:

• Global longitudinal strain ≤16% (absolute value), or
• E/e' ≥ 14.0 (average of medial and lateral velocities), or
• Diastolic dysfunction ≥ Grade II, or
• LVEF < 60%
• Stroke Volume Index < 35 ml/m²
• Anatomically suitable for transfemoral TAVR using the Medtronic Evolut PRO+ or Evolut FX system
• The subject and the treating physician agree the subject will return for all required follow-up visits

Key Exclusion Criteria:

• Age < 65 years
• LVEF ≤ 20% by 2-D echo
• Class I indication for cardiac surgery
• Contraindication for placement of a bioprosthetic valve
• Documented history of cardiac amyloidosis