Cardiorenal Syndrome: Critical Link Between Heart and Kidney Chris M. Bell, ACNP Cardiology Associates of North Mississippi Objectives Review the 5 Subtypes of the Cardiorenal Syndrome (CRS) Discuss the epidemiology and discriminating features of the CRS Assist in helping to understand the complexity of physiological, biochemical and neurohormonal derangements that complicate patient care Discuss treatment considerations in clinical management 1
Enrolled Discharges (%) 6/14/2016 Heart Failure Hits Home ACC/AHA Guidelines: Management of Fluid Status Patients should not be discharged from the hospital until a stable and effective diuretic regimen is established, and ideally, not until euvolemia is achieved Patients who are sent home before these goals are reached are at high risk of recurrence of fluid retention and early readmission because unresolved edema may itself attenuate the response to diuretics 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: J Am Coll Cardiol. 2009;53(15):1343-1382. doi:10.1016/j.jacc.2008.11.009 The dilemma we know what needs to be achieved but we have not been able to accomplish the desired outcome with any consistency or sustainability in many acutely decompensated heart failure patients Inadequate Diuresis During ADHF Treatment (Adhere Registry) 50 40 30 20 10 0 Note: For the chart, n represents the number of patients who have both baseline and discharge weight, and the percentage is calculated based on the total patients in the corresponding population. Patients without baseline or discharge weight are omitted from the histogram calculations. ADHERE Database 7% 6% 13% 24% 30% 15% Change in Weight (lb) Change in Weight From Admission to Discharge TheNation =26,757, 68% 3% 2% (<-20) (-20 to -15) (-15 to -10) (-10 to -5) (-5 to 0) (0 to 5) (5 to 10) (>10) 2
Renal Disease Affects Readmissions and Mortality Majority (71%) of CHF patients with SCr >2.5 mg/dl (10% of CHF patients) will be readmitted within 6 months 1 Concurrent renal disease, seen in 6.5% of acute CHF patients in a Canadian study, is a significant independent predictor of 30-day and 1-year mortality 2 1. Krumholz et al. Am Heart J. 2000;139:72. 2. Jong et al. Arch Intern Med. 2002;162:1689. Impact of Renal Function on Survival in HF Ibopamine Trial n=1906 Hillege et al. Circ. 2000; 102:203-210 Definitions Cardiorenal Syndrome (CRS) A condition in which there is dysfunction of both the cardiac and renal function Seen in heart failure patients who have renal dysfunction Seen in renal patients that develop cardiac dysfunction Risk Factors that increase chances for both HTN, Diabetes, Atherosclerosis 3
Schematic Overload Schematic Overload with more Arrows CRS Classifications Type 1 CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/ or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. Ronco C. Cardiorenal syndromes: definition and classification. Contrib Nephrol. 2010;164:33 38. Epub 2010 Apr 20 4
Type 1 CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/ or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. CRS Type I Key concepts Acute Generally, four broad subsets of heart failure 1 Acutely decompensated failure Hypertensive failure with preserved EF and pulmonary edema Cardiogenic shock Right ventricular failure Consider pre-existing risk factors, such as 2,3 Underlying renal insufficiency Worsening heart failure class Tachyarrhythmias Hypo/Hypertension High dose diuretic therapy Primary clinical observation is inadequate renal perfusion leading to low cardiac output with marked elevation of venous pressures resulting in renal congestion 1. Nohria A, et al. J Am Coll Cardiol. 2008;51(13):1268-1274. 2. Forman DE, et al. J Am Coll Cardiol. 2004;43(1):61-67. 3. Cowie MR, Eur Heart J. 2006;27(10):1216-1222. CRS Type I Treatment Considerations Decongestion if paramount If this is a relatively new condition the traditional approaches are often successful 1 Diuretics Vasodilators And, in the case of cardiogenic shock -- pressors If acute on chronic, then it is often more difficult due to refractory treatment responsiveness 2 1. Dickstein K, et al. 2010 Europace. 2010;12(11):1526-1536. 2. Pasquale Congest Heart Fail. 2007;13(2):93-98. 5
CRS Type 1 Treatment Considerations cont. Diuretics Loop diuretic preferred and intravenously Bolus vs Continuous Dose Trial 1 Augmented with low dose Dopamine DAD-HF 2 Ultrafiltration To Be or Not to Be 3,4,5 UNLOAD, CARRESS, AVOID-HF Up in the Air Consider plasma refill rate/hemoconcentration 6 1. Felker GM. New England Journal of Medicine. 2011;364(9):797-805. 2. Giamouzis G, J Card Fail. 2010;16(12):922-930. 3. Costanzo MR, J Am Coll Cardiol. 2007;49(6):675-683. 4. Bart BA, New England Journal of Medicine. 2012;367(24):2296-2304. 5. New England Journal of Medicine. 2013;368(12):1157-1160. 6. Testani JM, Circulation. 2010;122(3):265-272. CRS Type 1 Treatment Considerations cont. Vasodilators Nitroglycerin and nitropreside Limited data and cautious recommendations 1,2 Nesiritide Initially looked good but fell out of favor 3 1. Mullens W, 2008;52(3):200-207. 2. Yancy CW, et al. 2013 ACCF/AHA guideline J Am Coll Cardiol. 2013;62(16):e147-239. 3. Chen HH, Circ Heart Fail. 2013;6(5):1087-1094. CRS Type 1 Treatment Considerations cont. Inotropes/pressors More symptomatic relief, palliative measures, or bridge to decision overall associated with high morbidity and mortality, especially arrhythmogenic death 1 More novel agents 2,3 Vasopressin Levosimendan Relaxin 1. Yancy CW, et al. 2013 ACCF/AHA guideline J Am Coll Cardiol. 2013;62(16):e147-239. 2. Konstam MA, Jama. 2007;297(12):1319-1331. 3. Triposkiadis F, Expert Opin Investig Drugs. 2009;18(6):695-707. 6
Type 1 CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/ or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. CRS Type 2 Key Concepts Chronic abnormalities Cardiac is Primary (Type 2 and Type 4 are often very difficult to distinguish) Make an effort to discern which is primary cardiac vs renal Very few chronic heart failure patients present without some degree of renal dysfunction (ADHERE); furthermore, this co-existent relationship is associate with poor out comes. 1 1. Heywood JT, J Card Fail. 2007;13(6):422-430. CRS Type 2 Treatment Considerations Primary goal is evidence based care of the patient Aggressively prudent up-titration of ACE/ARB Hypotension, NSAIDS Carvedilol may have a more favorable effect on renal function 1 Spironolactone should be considered with attention to hyperkalemia How does PARADIGM fit into the CRS paradigm Possibly more favorable renal effects 2 Diuretics and diuretic resistance 1. Bakris GL, Kidney Int. 2006;70(11):1905-1913. 2. Solomon SD, Lancet. 2012;380(9851):1387-1395. 7
Elevated Neurohormone Levels Cause Diuretic Resistance Glomerulus Norepinephrine (and endothelin) decreases renal blood flow and GFR Proximal Tubule Angiotensin II increases sodium reabsorption Collecting Duct Aldosterone increases sodium reabsorption Krämer et al. Am J Med. 1999;106:90. 8
UNaV, meq/6 h 6/14/2016 CRS Type 2 Treatment Considerations cont Diuretic Resistence 1 Short-term (braking phenomena) Poorly understood Long-term distal nephron hypertrophy May be benefited by combination therapy 1. Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-395. Short-Term (Braking Phenomena) 300 250 200 150 100 50 0 Na + Excretion Net Diuresis After 4 Days of Rx = 0 ml Na + Intake Before F F1 F2 F3 F4 F = Furosemide Time, Days 1. Wilcox et al. Kidney Int. 1987;31:135. Na + Reaccumulation Between Furosemide Doses Long Term tolerance Tubular hypertrophy to compensate for salt loss Brater. N Engl J Med. 1998;339:387. 9
FENa,% 6/14/2016 Result of diuretic tolerance 20 18 16 14 12 10 8 6 4 2 Fractional Na Excretion Normal CRF CHF Secretory Defect 0 0.01 0.1 1 10 100 [Furosemide], µg/ml Ellison. Cardiology. 2001;96:132-143. Decreased Maximal Response Type 1 CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/ or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. 10
CRS Type 3 Key Concepts Acute Kidney Injury Contrast induced kidney injury Drug-induced nephropathies Kidney injury post major surgery Rhabdomyloysis Post-infectious glomerulonephritis CRS Type 3 Treatment Considerations Avoid the insult Assess for vulnerable patient populations Hydrate Novel therapies Avert System Technology (AVERT clinical trial (NCT 01976299) Type 1 CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/ or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. 11
CRS Type 4 Key Concepts Chronic abnormalities Renal vs Primary (Type 2 and Type 4 are often very difficult to distinguish) Principle concept is clinical management aimed at slowing the progression of renal dysfunction CRS Type 4 Treatment Considerations Appreciate the degree of renal insufficiency when considering medications and dosage, i.e. digoxin Be mindful of over diuresis Consider the possibility of chronic anemia No benefit in RED-HF(epo) 1 Interesting benefits of FAIR-HF (iron) 2 1. Swedberg K, N Engl J Med. 2013;368(13):1210-1219. 2. Anker SD, N Engl J Med. 2009;361(25):2436-2448. Type 1 CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/ or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. 12
CRS Type 5 Key Concepts Essentially, a simultaneous acute/chronic dysfunction of both the cardio and renal systems Limited studies and least understood; however, as more organs fail outcomes are obviously worse CRS Type 5 Treatment Considerations Prompt identification and treatment of the offending source Hydration Conservative vs Liberal 1 Pressor consideration Norepinephrine and vasopressor dopamine are both associated with high mortality but norepinephrine may have less adverse events 2 1. Wiedemann HP, N Engl J Med. 2006;354(24):2564-2575. 2. De Backer D, N Engl J Med. 2010;362(9):779-789. CRS Complicated Cardio-Renal Syndrome is very real and very complicated It is a marker for Advanced Management It is a tremendous burden leading to readmissions and death Effective treatment must be unique to the patient 13
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