A Prospective Randomized Trial of Furosemide-Induced High-Volume Diuresis with Matched Hydration Using a Dedicated Devic

1. A Prospective Randomized Trial of Furosemide-Induced High-Volume Diuresis with Matched Hydration Using a Dedicated Device to Prevent Contrast NephropathyThe MYTHOS Trial Antonio L. Bartorelli, MD Centro Cardiologico Monzino Department of Cardiovascular Sciences University of Milan Italy

2. Disclosure Statement of Financial Interest Consulting fees/Honoraria Speaker’s bureau Speaker’s bureau Abbott Vascular Johnson & Johnson Cordis Bracco

3. Background (I) Contrast-induced nephropathy (CIN) is a frequent complication of diagnostic and interventional procedures, associated with in-hospital and long-term unfavorable outcomes Intravenous hydration with isotonic saline solution has been shown to protect against CIN However, hydration is usually performed at a rate significantly lower than that shown to provide protection for logistic reasons and fear of over-hydration and pulmonary edema, particularly in patients with reduced LV function This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

4. Background (II) Diuretics have been used to prevent over-hydration and to protect the kidney against CIN by: Increasing urine flow that results in greater contrast dilution within the renal tubules and lower direct kidney toxicity Reducing medullary ischemia due to decreased tubular sodium re-absorption and, consequently, oxygen consumption However, by decreasing intravascular volume diuretics may induce vasoconstriction (a mechanism involved in CIN pathogenesis) and may exacerbate that produced by contrast agent itself, thus increasing CIN risk (Solomon et al. NEJM 1993) If we were able to maintain the positive effects of diuretics and at the same time counteract their adverse effects, we could possibly shift our balance toward an overall benefit in terms of CIN prevention This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

5. Study Purpose The aim of the MYTHOS trial was to evaluate if furosemide-induced high-volume diuresis with concurrent maintenance of intravascular volume may prevent CIN in high-risk patients To this purpose, we investigated the effect of a new CIN preventive strategy based on a dedicated device (RenalGuard System), which is able of delivering i.v. saline solution in an amount automatically matched to the volume of urine produced in response to an i.v. bolus of furosemide

7. RenalGuard System

8. Study Protocol

9. Study Protocol Exclusion criteria: Primary/rescue PCI Cardiogenic shock Overt CHF Acute respiratory failure Chronic dialysis Known to be unsuitable for Foley catheter placement Renoprotective drugs were not administered A non-ionic, low-osmolar contrast agent (Iomeron) was used in all patients

10. Study Protocol

11. Baseline Clinical and Procedural Characteristics RenalGuard Control P value Group (n=80) Group (n=77) Age (yrs) 72?7 74?8 NS Men 64 (80%) 61 (70%) NS Weight (kg) 76?14 73?12 NS Smokers 28 (35%) 32 (42%) NS Diabetes mellitus 33 (41%) 25 (32%) NS Hypertension 64 (80%) 64 (83%) NS Dyslipidemia 56 (70%) 43 (69%) NS Prior MI 39 (49%) 31 (40%) NS Prior CABG 24 (30%) 18 (23%) NS Prior PCI 44 (55%) 30 (39%) NS Elective PCI 45 (56%) 49 (64%) NS Urgent PCI 35 (44%) 28 (36%) NS Mean LVEF (%) 52?12 52?13 NS Serum creatinine (mg/dl) 1.8?0.6 1.7?0.5 NS eGFR (ml/min/1.73 m2) 38?11 41?10 NS Sodium (mEq/l) 140?2 139?3 NS Potassium (mEq/l) 4.1?0.8 4.4?0.6 NS Hemoglobin (g/dl) 12.2?1.8 12.3?1.8 NS Coronary angiography 80 (100%) 77 (100%) NS PCI 44 (55%) 48 (62%) NS Contrast volume (ml) 188?106 206?112 NS ACE-inhibitors 50 (62%) 54 (70%) NS Aspirin 70 (88%) 71 (92%) NS Diuretics 44 (55%) 43 (56%) NS Peri-PCI bleeding 3 (4%) 2 (3%) NS

12. Incidence of CIN Added the patient numbers at the top of each columnAdded the patient numbers at the top of each column

13. In-Hospital Complications RenalGuard Control P value Group Group (n=80) (n=77) CIN requiring RRT 1 (1.2%) 3 (4%) NS Acute myocardial infarction 0 (0%) 1 (1.3%) NS Atrial fibrillation 0 (0%) 2 (3%) NS Emergency CABG 0 (0%) 0 (0%) NS Acute heart failure 5 (6%) 9 (12%) NS Hypotension/shock 0 (0%) 0 (0%) NS In-hospital death 1 (1.2%) 3 (4%) NS All clinical events 7 (9%) 18 (23%) 0.012

14. Composite End Point (CIN and MACE) Added the patient numbers at the top of each columnAdded the patient numbers at the top of each column

15. Conclusions Maintenance of intravascular volume after furosemide-induced forced diuresis can be safely and effectively obtained with the RenalGuard System This preventive strategy significantly reduced the incidence of CIN and in-hospital MACE in CKD patients undergoing PCI The positive results were mainly driven by the effect obtained with this treatment in NSTEMI patients undergoing urgent (<24 hrs) PCI

16. A New Concept is Emerging for CIN Prevention The hydration volume should be commensurate to the patient’s risk A high volume (~1 L/hr) of controlled hydration is likely required in high-risk patients This goal can be achieved by: Exactly matching fluid removal to high-volume i.v. hydration to prevent fluid overload (Hemofiltration) Exactly matching i.v. hydration to furosemide-induced high-volume diuresis to avoid hypovolemia (RenalGuard)