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The 1st Kuwait-North American Update in Internal Medicine Acute Decompensated Heart Failure in Hospitalized Patients Michael M. Givertz, M.D. Medical Director, Heart Transplant/Mechanical Circulatory Support Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, MA Heart Failure is a Progressive Disease The Course of Heart Failure Goodlin et al., J Am Coll Cardiol 2009;54:386 Trends in ADHF Morbidity/Mortality Mortality 09 20 08 20 07 20 06 20 05 20 04 20 03 20 02 20 01 20 00 20 99 35 30 25 20 15 10 5 0 19 Hosp Rate per 1000 1-Yr Mortality, % HF Hosp Year Chen et al., JAMA 2011;306:1669 Markers of Advanced Disease and Poor Prognosis • • • • • • • Severe (objective) exercise intolerance ACE inhibitor or β-blocker intolerance High-dose diuretics RV failure, 2 pulmonary hypertension Hyponatremia, anemia, hyperuricemia Chronic kidney disease (CKD) Cardiac cachexia Muscle Wasting in Heart Failure Repeat Hospitalizations and Death 6-12 months Setoguchi et al., Am Heart J 2007;154:260 ADHF: Who are They? • • • • • Older (mean age 70s) ≈50% women 40-50% preserved EF Over 85% with chronic HF Multiple co-morbidities – Hypertension – Diabetes – Chronic kidney disease Shortness of Breath is the Main Reason for HF Hospitalization Congestion (Not Low Output) is the Main Finding in Hospitalized Patients Systolic blood pressure (%)1 > 140 mm Hg 50 90 – 140 mm Hg 48 < 90 mm Hg 2 Mean heart rate (bpm)2 PCWP (mm Hg)2 Cardiac index2 1Fonarow ≈90 25 – 30 Usually preserved et al. Rev Cardiovasc Med 2003;4 Suppl 7:S21 2VMAC Investigators. JAMA 2002;287:1531 Congestion is Often Unrecognized and Precedes Hospitalization PASP PADP HR Adamson et al., J Am Coll Cardiol 2003;41:565 Yu et al., Circulation 2005;112:841 CardioMEMS: Pressure Measurement System Dear Michael M. Givertz, MD A new reading has come in for your patient, 31-003 C-Z which violated the alert threshold set up for "Mean Pressure above 20.0 mmHg". The reading was taken on 25 Jan 04:06 EST. Systolic: 89 Diastolic: 51 Mean: 66 Heart Rate: 91 Pressure waveform is attached. Thank you, CardioMEMS Alert System CHAMPION Study: HF Hospitalizations 260 HF Hospitalizations, no. 240 Treatment Control 220 p < 0.001, based on Negative Binomial Regression 200 180 160 140 120 100 80 60 40 6 Months 15 Months 20 At Risk 0 Treatment 0 270 Control 280 90 262 267 180 244 252 270 209 215 360 168 179 450 130 138 540 107 105 630 81 67 720 28 25 810 5 10 900 1 0 ACC/AHA Guidelines for ADHF Guidelines N=25 Class I N=18 Class II N=5 Evidence A N=1 IIa N=4 Class III N=2 IIb N=1 Evidence B N=2 Consensus opinion 72%, “Evidence” 28% Evidence B N=3 Evidence B N=1 Evidence C N=14 Evidence C N=3 Evidence C N=1 Class I, Level of Evidence A • Concentrations of BNP1 or NT-proBNP2 should be measured in patients being evaluated for dyspnea in which the contribution of HF is not known. diagnosis requires Unfortunately, theFinal routine use of serial natriuretic interpreting these results in thehemodynamics context of all has peptide measurements to monitor available clinical andinought not to the be not been shown to be data helpful improving considered stand alone patient test. with HF outcomes of theahospitalized (ACC/AHA) 1Maisel et al., N Engl J Med 2002;347:161 (BNP Study) 2Januzzi et al., Am J Cardiol 2005;95:948 (PRIDE Study) Diuretics for ADHF and Fluid Overload • Treatment with IV loop diuretics should begin • • in the ED without delay, as early intervention may be associated with better outcomes (Level of evidence B). If patients are already receiving loop diuretics, initial IV dose should equal or exceed chronic oral dose (Level of evidence C). When a patient with congestion fails to respond to IV diuretics, consider increased dose of loop diuretic, addition of second diuretic, continuous infusion of loop diuretic (Level of evidence C) DOSE Study Felker et al., N Engl J Med 2011;364:797 DOSE Study • • • 308 patients with ADHF Randomized 2x2 to low vs. high-dose furosemide and IV bolus vs. continuous infusion No differences at 72 hours in: – Global symptom assessment (1° efficacy endpoint) – Change in renal function (1° safety endpoint) Felker et al., N Engl J Med 2011;364:797 Death, Rehospitalization, or ED Visit Felker et al., N Engl J Med 2011;364:797 Secondary Endpoints: Low vs. High Dose Strategy Low High P value Dyspnea VAS AUC at 72 hours 4478 4668 0.041 % free from congestion at 72 hrs 11% 18% 0.091 Change in weight at 72 hrs -6.1 lbs -8.7 lbs 0.011 Net volume loss at 72 hrs 3575 mL 4899 mL 0.001 Change in NTproBNP at 72 hrs (pg/mL) -1194 -1882 0.06 % Treatment failure 37% 40% 0.56 % with Cr increase > 0.3 mg/dL within 72 hrs 14% 23% 0.041 6 5 0.55 Length of stay, days (median) Cardiorenal Syndrome: Worsening Renal Function During Treatment of ADHF • • • Increase in creatinine ≥ 0.3 mg/dl Occurs in 15-30% of admissions Risk factors: – Older age – HTN, DM – Baseline renal dysfunction • May be associated with adverse outcomes during the hospitalization and post-discharge Gottlieb et al., J Card Fail 2002;8:136 Forman et al., J Am Coll Cardiol 2004;43:61 Transient vs. Persistent Worsening Renal Function N = 467 with ADHF, WRF in 115 (24%) +1.17 +0.60 Aronson et al., J Card Fail 2010;16:541 Ultrafiltration: An Attractive Alternative to Diuretics • More effective way to restore sodium balance1 – removal of isotonic vs. hypotonic saline • • • • No effect on serum electrolytes Rapid and predictable fluid removal Does not stimulate neurohormones May restore diuretic responsiveness and improve long-term outcomes2 1Jessup and Costanzo, J Am Coll Cardiol 2009;53:597 2Agostoni et al., J Am Coll Cardiol 1993;21:424 Minimally Invasive Ultrafiltration • • • • FDA approved, portable device Non-ICU, routine nursing PICC or central line UNLOAD (sponsor-initiated) – Greater weight loss at 48 hours compared to IV diuretics (5 vs. 3.1 kg; p < 0.001) – Decreased HF hospitalization at 90 days Costanzo et al., J Am Coll Cardiol 2007;49:675 CARRESS Study N = 188 with ADHF, Cre ↑ ≥ 0.3, persistent congestion Randomized to UF vs. stepped pharmacologic care Bart et al., N Engl J Med 2012;367:2296 CARRESS Study: Primary Endpoint Cre ↑ 0.23 Cre ↓ 0.04 Bart et al., N Engl J Med 2012;367:2296 CARRESS: Adverse Events • More patients in UF group (72%) had SAEs compared to stepped pharmacologic care (57%) – Renal failure – Bleeding – IV catheter-related • No difference in 60-day mortality or rate of death or HF rehospitalization Bart et al., N Engl J Med 2012;367:2296 Options for Diuretic Resistant Patients • Vasodilators – IV Nitroprusside, nitroglycerin – Hydralazine/nitrates • Positive inotropes – Dobutamine – Milrinone – Dopamine (renal-dose vs. higher doses) • Mechanical circulatory support Dobutamine: Interpatient Variability Colucci et al., Circulation 1986;73:III175 Tolerance to (Not All) Inotropes N = 20, severe chronic HF, CI 1.63 L/min/m2 Mager et al., Am Heart J 1991;121:1974 Is There Really a Role for Low-Dose Dopamine? N = 380 with ADHF and estimated GFR 15-60 ml/min Randomized to dopamine 2 mcg/kg/min vs. placebo Chen et al., JAMA 2013:310:2533 Low Dose Dopamine: Co-primary End-points ROSE Study 72 Hour Urine Volume Change in Cystatin-C No effect on symptoms, 60-day readmission or 180-day mortality More tachycardia Chen et al., JAMA 2013:310:2533 Worst Prognosis with Inotrope Dependence Community-based Clinical trial Hershberger, J Card Fail 2003;9:180 Rogers, J Am Coll Cardiol 2007;50:741 ADHF is a Good Time to Address Risks and Co-Morbidities • • • • Arrhythmias or conduction disease – consider ICD for primary prevention – AF: consider amiodarone/CV, ablation – LBBB: consider CRT* Risk of thromboembolism: need for anticoagulation or anti-platelet therapy Anemia, diabetes, obesity, sleep apnea Advanced directives *should NOT be used as a “bail-out” Dying with HF is Rarely Unexpected • • • • • N = 160 Mean age 60, 74% male Mean duration of HF: 5 years 40% died in hospital, 10% with hospice Within 6 months of death: – 93% NYHA class III or IV – 74% hospitalized at least once – mean Na 128, Cre 3.1, Hct 30 Teuteberg et al, J Card Fail 2006;12:47 Comprehensive Discharge Instructions Six key aspects of care • • • • • • Diet Medications (adherence and uptitration) Activity level Follow-up appointments Daily weights What to do if HF worsens? Thank you for your attention