1 / 58

The Cardio-Renal Syndrome Stephen L. Rennyson MD

The Cardio-Renal Syndrome Stephen L. Rennyson MD. Clinical Presentation. 68 y.o. man with iCMO admitted with volume overload consistent with CHF exacerbation Admitted 2 weeks prior -- similar presentation Discharged with appropriate CHF regimen, furosemide diuretic. Laboratory Studies

farrah
Download Presentation

The Cardio-Renal Syndrome Stephen L. Rennyson MD

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. The Cardio-Renal SyndromeStephen L. Rennyson MD

  2. Clinical Presentation • 68 y.o. man with iCMO admitted with volume overload consistent with CHF exacerbation • Admitted 2 weeks prior -- similar presentation • Discharged with appropriate CHF regimen, furosemide diuretic • Laboratory Studies • Sodium 132 • Creatinine 1.8 • Hemoglobin 9.8 • Albumin 2.2

  3. Placed on BiPap in the ED, given 120 mg of iv Lasix, transferred to CICU . . . Started NTG gtt • Initial success of 500 cc urine output • Morning laboratory studies show creatinine rising • Midnight dose of lasix produced little urine output • Blood pressure falling . . .

  4. Cardio-Renal Syndrome Background Pathophysiology Management Options Case

  5. Congestive Heart Failure • Epidemiology changing from acute management to managing the chronicity of cardiac dysfunction • An indicence of 5 million persons • Responsible for over 1 million yearly hospitalizations • 280,000 deaths annually

  6. Comorbid Conditions . . .Associated with a worse prognosis • Anemia (Hb < 10.0) • Cirrhosis • Peripheral Vascular Disease • Hyponatremia (<135) • Renal failure N Engl J Med 2006; 355:260-269July 20, 2006

  7. Cardiovascular Outcomes with renal dysfunction • Stratified by GFR Cumulative incidence • Cardiovascular death • Unplanned ADHF admission reduced LVEF (LVEF<=40%) • Stratified by GFR LV systolic function (LVEF>40%) Hillege, H. L. et al. Circulation 2006;113:671-678

  8. ADHERE Registry • Registry of Acute Decompensated Heart Failure (ADHF) • 105,000 patient registry • QOC study evaluating variations in CHF treatment • Best predictors of outcome: • BUN • Creatinine

  9. Cardio-Renal Syndrome • Most Simplistic Description: • Associated loss of renal function in the setting of advanced CHF • CRS or RCS?

  10. Subtypes • Type I, acute CRS • Type II, chronic CRS • Type III, acute renocardiac syndrome • Type IV, chronic renocardiac syndrome • Type V, secondary CRS -- sepsis, amyloidosis

  11. Cardio-Renal Syndrome • CHF patients at increased risk for CRS: • Hypertension • Diabetes • Severe Vascular Disease • Elderly

  12. Cardio-Renal Syndrome Background Pathophysiology Management Conclusions

  13. Pathophysiology • Neurohormonal Factors: • SNS, RAAS, AVP System • Hemodynamics: • Loss of Cardiac Output • Transrenal perfusion pressure • Intrarenal hemodynamics

  14. Neurohormonal Axis Adenosine

  15. CHF Hemodynamics • Systolic or Diastolic CHF • Exacerbations -- Symptomatology seen objectively • Elevated PCWP • Elevations of INR, Alkaline Phosphatase • Elevations of Creatinine • Shift in paradigm

  16. CVP and Renal Failure • 2,557 patients underwent RHC • Age 59 ± 15 years • 57% were men • Renal Function using estimatedGlomerular Filtration Rate (eGFR) Damman, K. et al. J Am Coll Cardiol 2009;53:582-588

  17. Curvilinear Relationship Between CVP and eGFR According to Different Cardiac Index Values Solid line = cardiac index <2.5 dashed line = cardiac index 2.5 to 3.2 dotted line = cardiac index >3.2 p = 0.0217 Central Venous Pressure Damman, K. et al. J Am Coll Cardiol 2009;53:582-588

  18. CVP and Renal Failure Kaplan-Meier Analysis of Event-Free Survival According to Tertiles of CVP Damman, K. et al. J Am Coll Cardiol 2009;53:582-588

  19. Renal Hemodynamics • Transrenal perfusion pressure • TRPP = MAP - CVP • CVP influenced: • PAP -- Oxygenation, Valve Dysfunction, CO • Volume Status • MAP -- Perfusion Pressure • Cardiac Output • Systemic Vascular Resistance

  20. Renal Hemodynamics • Ultimately lack of adequate transrenal perfusion pressure: • Renal Hypoxia • Inflammation / Cytokine Release • Progressive loss of nephron function and structural • Activation of the Neurohormonal cascade

  21. Cardio-Renal Syndrome Background Pathophysiology Management Options Case

  22. The Cardio-Renal Syndrome • Treatment Goals • Same goals as ADHF • Removal of Volume • Optimizing Hemodynamics • Complicated by chronic renal failure and acutely worsening renal function

  23. Removal of Volume • Loop Diuretics • Brain Naturetic Peptide • Arginine Vasopressin Antatonism • Adenosine Antagonism • Ultrafiltration

  24. Loop Diuretics • Goal --> Deplete extracellular fluid volume • Balanced refilling interstitium to intravascular compartment • Reality --> Contraction of circulating volume --> Activation of neurohormonal response

  25. Loop Diuretics • Furosemide • Blockage of the thick ascending loop Na/ K/ 2 Cl pump • Acts intraluminally • Travels Bound to albumin • High Na delivered to distal tubules • Chronic use -> cellular hypertrophy -> increased Na reabsorption -> Failure of diuresis

  26. Diuretic Resistance • Inadequate dosing • Cellular Hypertrophy • Bolus vs Continuous Infusion • Double Diuretic Therapy • Nutritionally Deficient Patients

  27. Loop Diuretic Dosing • Dose response curve is not smooth • Thus, no diruresis until threshold dose reached • If 20 mg IV once a day is insufficient; BID will be just as ineffective • Torsemide and Bumetanide vs Furosemide • Similar iv bioavailabiltiy • Improved Oral Bioavailablity

  28. Braking Phenomenon • Short term tolerance after the first dose • Continuous Infusion • Limited Data • Cochrane Review • Improved safety • Improved diuresis • Shorter Hospital Stay • Lower Cardiac Mortality in a single study Cochrane Database Syst Rev. 2004. p. CD003178.

  29. The DOSE TrialDiuretic Optimization Strategies Evaluation • DOSE Trial • 308 patients with ADHF • Low vs High Dose Furosemide • Continuous vs a12 hour dosing • Overall no significant difference among all groups • Patients symptoms • Creatinine • High Dose group had a greater diuresis with transient increases in creatinine N Engl J Med. 2011 Mar 3;364(9):797-805.

  30. Diuretic Resistance • Double Diuretic Therapy or Sequential Nephron Blockade • Loop + Thiazide • Chlorothiazide 250 mg vs 500 mg IV / Metolazone 5-10 mg PO • Very Effective -- Weight loss and edema resolution • Double Sodium Excretion • CAUTION: Hyponatremia, Hypotension, Worsening renal function • Chronic use -> cellular hypertrophy -> increased Na reabsorption -> Failure of diuresis J Am Coll Cardiol, 2010; 56:1527-1534, doi:10.1016/j.jacc.2010.06.034

  31. Diuretic Resistance • Travels bound to albumin --> Delivered to Glomerulus --> Filtered --> Acts luminal side of thick ascending loop • Advanced CHF / Chronically ill • Elevated catecholamines (Catabolic) • Low serum albumin • Decreased delivery of diuretic to renal tubules **Addition of salt poor albumin** Furosemide-Albumin dimer allows better drug delivery Clin Pharmacokinet. 1990 May;18(5):381-408

  32. Brain Natriuretic Peptide LV volume overload --> Cardiac Myocytes secrete BNP precursor --> Converted to proBNP --> ProBNP cleaved into: • C-terminal BNP (biologically active) • Decrease in SVR and CVP • Increase natriuresis • N-terminal BNP or NT-proBNP (biologically inactive)

  33. Nesiritide (Natrecor) • New to market in 2001 • Actions in ADHF • PCWP reduced within 15 minutes of administration • Resultant decreases in PA and RA pressure • Reduced SVRI • Resultant increase in CO • Enhances loop diuretic effects • Modest intrinsic natriuretic and diuretic effects • No tachyphylaxis • Blocks loop diuretic effects of aldosterone up-regulation • Cleve Clin J Med. 2002 Mar;69(3):252-6. Review • Clin Cardiol. 2010 Jun;33(6):330-6

  34. ASCEND-HF • Over 7000 patients with ADHF -- standard therapy • Nesiritide infusion 24 hrs - 7 days vs placebo • Primary End points: • CHF mortality and readmission (30 days) • Self reported Dyspnea at 6 and 24 hours

  35. ASCEND-HF

  36. ASCEND-HF • Role of Natrecor: • Resolved Concerns: • Worsening mortality • Worsening renal function • No significant benefit compared to standard therapy • Improved Dyspnea Score ($500.00/day)

  37. Arginine Vasopressin • Arginine vasopressin (AVP), secreted by posterior pituitary • V1 Vascular receptor • V2 Renal receptor • Proportional to the severity of HF • Contributes to fluid retention and hyponatremia

  38. Hyponatremia

  39. ACTIV Trial • Initial trial for Tolvaptan -- AVP antagonist • 319 patients with systolic dysfunction (<40%) admitted with exacerbation • Tolvaptan vs Placebo/ Standard Treatment • Greater loss of body weight • Greater urine output at 24 hours • Increase in serum sodium JAMA. 2004 Apr 28;291(16):1963-71.

  40. EVEREST Trial • Efficacy of Vasopressin Antagonism in HF Outcome Study With Tolvaptan • Over 4000 patients in two separate study groups • EF < 40% • Tolvaptan (30mg) vs Placebo in combination with standard HF thearpy • Treatment time up to 7 days JAMA. 2007 Mar 28;297(12):1332-43. Epub 2007 Mar 25

  41. EVEREST Trial JAMA. 2007 Mar 28;297(12):1332-43. Epub 2007 Mar 25

  42. EVEREST Trial JAMA. 2007 Mar 28;297(12):1332-43. Epub 2007 Mar 25

  43. EVEREST Trial JAMA. 2007 Mar 28;297(12):1332-43. Epub 2007 Mar 25

  44. EVEREST Trial • No change over 24 month follow up: • All Cause Mortality • Cardiovascular Mortality • Heart Failure Hospitalization JAMA. 2007 Mar 28;297(12):1332-43. Epub 2007 Mar 25

  45. Adenosine?? • Elevated levels seen in ADHF • Released locally in response to stress (Macula Densa) and sodium delivery to the DCT • Actions: • Afferent Arteriole Vasoconstriction • Decreased GFR • Sodium reabsorption • Tubuloglomerular feedback mechanism for regulation of GFR

  46. Adenosine • Tubuloglomerular Feedback • Acute delivery of sodium to the distal tubules (Lasix) • Adenosine further released from the macula densa • Further renal dysfunction Br J Pharmacol. 2003 August 2; 139(8): 1383–1388.

  47. Adenosine AntagonismBG9719 • 63 patients with ADHF • Compared Groups • Lasix Alone • Adenosine Antagonist Alone • Combination thearpy Circulation. 2002;105:1348-1353

  48. Adenosine Circulation. 2002;105:1348-1353

  49. Ultrafiltration • The removal of isotonic volume across a semipermeable membrane • Hemodialysis -- Removal of volume and solutes using a concentration gradient • UF does not decreasesodium presentation to the macula densa • Avoids neurohormonallymediated sodium and water reabsorption

More Related