ISCHEMIA-CKD Trial Optimal Revascularization Therapy

1. ISCHEMIA-CKD TrialOptimal Revascularization Therapy

2. Goal • Revascularization of all ischemic myocardial segments (detected by non-invasive imaging or by fractional flow reserve (FFR) testing) within 4 weeks after treatment assignmentwhile minimizing the risk of contrast induced acute kidney injury (AKI)

3. Risk of Contrast Induced Acute Kidney Injury Acute kidney injury (AKI) was defined as serum creatinine increase of 25% and/or 0.5 mg/dl Exponential increase in the risk of contrast induced AKI with eGFR <40 McCullough et al. J Am Coll Cardiol 2008;51:1419–28

4. Mantra to prevent contrast induced AKI • Hydration!! Hydration!! Hydration!! • Use ultra low-volume contrast protocol for cath and PCI • Use IVUS-guided PCI • Cath and PCI can be done with as little as 20-30 cc of contrast • Avoid nephrotoxic agents • Consider staged procedure as needed

5. Hydration Protocol used in POSEIDON trial: • Initiate 3mL/kg/h of normal saline IV, for at least 1 h prior to angiography • Measure LVEDP prior to contrast administration • Adapt infusion rate based on LVEDP measurement as follows: • 5 mL/kg/hr for LVEDP < 13 mm Hg • 3 mL/kg/hr for LVEDP of 13 mm Hg to 18 mm Hg • 1.5 mL/kg/hr for LVEDP > 18 mm Hg • Continue fluid administration for 4 hours post procedure

6. Hydration Simplified protocol based on LVEF (expert opinion): • Patients with preserved EF • IV 0.9% NS at 1 cc/kg/hour for 12 hours pre- and post-procedure • Patients with EF<40% • IV 0.45% NS at cc/cc replacement (match urine output to maintain euvolemia) for 12 hours pre- and post-procedure

7. Ultra-low volume contrast techniques • Use small diameter catheters (i.e., 5–6 F) without side-holes • All contrast injections require simultaneous cine angiogram, i.e., ‘‘no dye without the cine’s eye’’ • Limit the volume of contrast injected to 1–2 cm3 per injection using a 3-cm3syringe • During PCI, prior to exchange of devices such as balloon catheters, remove contrast from the guide catheter by back bleeding contrast out of the ‘‘Y’’ connector

8. Ultra-low volume contrast techniques • If available, display previous angiographic images alongside active fluoroscopy screen as a reference to use as guidance during guide wire, balloon, stent and ultrasound passage • Absolutely no contrast ‘‘puffing’’/test injections during the procedure • Use IVUS liberally for pre-PCI assessment of the lesion, selection of therapeutic modalities, and post-PCI result assessment (IVUS guided PCI)

9. Ultra-low volume contrast techniques • Use biplane angiography when available • Avoid ventriculography • Pre-procedure statins if not already on statin therapy • Use iso- or low-osmolar contrast media (besides iohexol and ioxaglate) • Hold diuretics pre-procedure in euvolemic participants and those unlikely to have heart failure precipitated by administration of radiocontrast media • Avoid nephrotoxic agents prior to the procedure and at least 48 hours post procedure

10. CABG vs. PCI • Low SYNTAX score (0-22): PCI or CABG • Intermediate SYNTAX score (23-33): CABG preferred • High SYNTAX score (>33): CABG strongly preferred Consult ‘Heart-kidney’ team (Non invasive cardiologist, interventionalist, surgeon, and nephrologist) as needed Decision should also be based on renal transplant considerations for the participants based on local practices

11. Other Aspects of ORT • Given the increased risk of restenosis, the use of DES is favored in participants with advanced CKD (such as everolimus and zotarolimus-Resolute) • Emphasis on ischemia guided revascularization (decreases volume of contrast used) • For antiplatelet/anticoagulant choice, FFR use, stent choice, deployment technique and other aspects of ORT- please refer to ORT slideset/MOO for the main ISCHEMIA trial