Tips & tricks on how to treat an acute heart failure patient with low cardiac output and diuretic resistance

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1 Tips & tricks on how to treat an acute heart failure patient with low cardiac output and diuretic resistance J. Parissis Attikon University Hospital, Athens, Greece

2 Disclosures ALARM investigator received research grants by Abbott US and Orion Pharma Received horonaria for advisory boards and lectures from Novartis and Servier

3 Patient profile Demographics and risk factors 65 year-old female Admitted April 2014 Cardiovascular risk Chemotherapy for Breast Cancer (regimen including doxorubicin)

4 Patient profile Cardiovascular history First heart failure diagnosis in 2012 Coronary arteriography negative for CAD in 2012 NYHA II, 2012 Mild renal failure Creatinine 1.6 mg/dl (NR ) Chronic anemia Haemoglobin 10.5 g/dl (NR 14-18) Hospitalized for decompensation in January 2014

5 Chronic medications prior to admission With treatment, stable for 2 months Low sodium diet; regular exercise; daily weight measurements Medical therapy Enalapril 10 mg Furosemide 80 mg PO Spironolactone 50 mg Bisoprolol 5 mg Warfarin 5 mg QD (episodes of AF)

6 Clinical evaluation at outpatient clinic (referral) Early April (10 wks after last hospitalisation) Decreased exercise tolerance (NYHA III) Increased furosemide mg/day Evaluated for CRT

7 ER evaluation- NYHA-IV Next two weeks (mid April) Symptom worsening Progressive dyspnoea Weight gain 5 kg ER admission NYHA-IV 23 April 2014

8 ER Physical exam results General Dyspnoea at rest Vital signs BP 100/65 mm Hg HR 101 bpm RR 24 ipm Neck Jugular vein distension Lungs Rales over the lung bases Heart S2P > S2A; S3 at apex Abdominal Liver enlarged 3 cm; mild ascites Extremities Oedema of lower extremities Cool extremities +

9 Admission ECG

10 Admission echocardiogram Left atrium: 63 mm (NR, 20 40) LVEDD: 76 mm (NR, 35 56) LVESD: 66 mm (NR, 25 40) LVEF, Simpson: 25% (NR > 55 %) Long axis Systole LV RV AV Mitral insufficiency 2-3+/4 Aortic insufficiency 1+/4 MV LA Tricuspid insufficiency 2+/4 Pulmonary hypertension (estimated pulmonary pressure = 60 mmhg)

11 Admission laboratory tests Urea Creatinine Sodium Potassium Hemoglobin BNP Arterial blood gas 165 mg/dl (NR=10-20 mg/dl) 2.3 mg/dl (NR= mg/dl) 131 meq/l (NR= meq/l) 3.54 meq/l (NR= meq/l) 11.2 mg/dl (NR=14-18 mg/dl) 1050 pg/ml ph 7.48 (NR = ) PO 2 64 mm Hg (NR= mm Hg) PCO 2 28 mm Hg (NR=35-45 mmhg) HCO3-21 meq/l (NR=21-28 meq/l) INR 2.7 (NR= )

12 Case summary History 65 year-old female 2-year known history of HF due to dilated cardiomyopathy Presentation Mild chronic anaemia SBP 100 mmhg Worsening HF in the last 2 weeks NYHA IV Acutely aggravated renal dysfunction Pulmonary and systemic congestion

13 What would you do? A. Start IV diuretics B. Start infusion of an inotropic agent C. Put on IV vasodilator D. 1 & 2 E. 1& 3

14

15 Admission to the ward Initial treatment Bed rest, fluid restriction Oxygen by nasal cannula Correct potassium level IV diuretics (furosemide 40 mg iv bolus initially, and continuous infusion at least equal dose of oral regimen) ACE inhibitor discontinued Bisoprolol dose cut by 50% Kept MRA

16 After 3 hours Evolution in ward No significant improvement Worsening dyspnoea (oxygen saturation 89%) Rales over 2/3 of lungs Stable blood pressure: 100 / 60 mm Hg Decreased urine output Admitted to CCU (Hemodynamic monitoring)

17 CCU chest X-Ray

18 Hemodynamic measures in CCU Parameters measured MAP: 82 mm Hg (NR >70) CI: 1.91 L/min/m 2 (NR ) SVRI: 2092 dyne-sec/cm 5 (NR ) PVRI: 962 dyne-sec/cm 5 (NR ) PCWP: 32 mm Hg (NR 5-15) RAP: 22 mm Hg (NR 0-8) SvO 2 : 60 % (NR >70%)

19 What would you do now? ADD: A. Oral metolazone B. Dopamine C. Dobutamine D. Levosimendan E. Attempt haemofiltration F. Mechanical support

20 Management of the patient with diuretic resistance in ADHF: general concepts-esc guidelines 2012 Restrict water and salt intake Maximize effects of neurohormonal antagonists Optimize diuretic dosing and route/ combine diuretics Combine diuretics with vasoactive therapies that improve peripheral perfusion (according to SBP) Consider renal-specific therapies in selected patients - reno-protective inotropes: dopamine, levosimendan - Ultrafiltration and/or hemodialysis Investigational therapies - hypertonic saline plus high-dose loop diuretics - vasopressin antagonists (hyponatremia) - adenosine antagonists - serelaxin Consider IABP/ LVADs

21 Patient profiles for inotropic therapy Hemodynamic impairment with low cardiac output (i.e. CI < 2.0 Lt/min/m2) and increased left and/or right ventricular filling pressures [i.e. PCWP (18 20 mmhg) and RAP (10 12 mmhg)]. Critical patient s conditions caused by abnormal hemodynamics and including any of the following: a. Severe exercise limitation b. Diuretic resistant fluid overload c. Kidney and/or liver dysfunction as shown by abnormal laboratory exams (serum creatinine, BUN, bilirubin,etc.) Teerlink J, Metra M, et al. Heart Fail Rev 2009;14:

22 In-hospital mortality Short-term Survival by Treatment Among Patients Hospitalized with Acute Heart Failure: The Global ALARM-HF Registry Using Propensity Scoring Methods Inotropes Whole cohort Diuretics Vasodilators Mebazaa A, Parissis J, Porcher R, et al. Intensive Care Med 2011;137: Days

23 Probability of Surviving SURVIVE 180-day All-Cause Mortality Levosimendan Dobutamine p= Days Since Start of Study Drug Infusion Mebazaa et al. JAMA 2007;297:

24 Hazard Ratios for Patients on b-blockers at Baseline Appeared to Favor Levosimendan Day, Group Bohm et al. Crit Care Med May;39(5): Favors Levosimendan Favors Dobutamine Interaction p-value 5 b-blocker users* b-blocker non-users 14 b-blocker users* b-blocker non-users 31 b-blocker users* b-blocker non-users 90 b-blocker users* b-blocker non-users 180 b-blocker users* b-blocker non-users p-value = * Within 24 hours of study drug infusion Hazard Ratio (95% CI)

25 Current IV Inotropic Therapies in AH: ESC Guidelines 2012 Dobutamine: cl IIa, Level evidence B (prefereble agent due to lower cost) Levosimendan: cl IIb, Level of evidence B (preferable agent for patients on beta blocker) PDEIs: cl IIb, Level evidence Β Dopamine: cl IIb, Level evidence B

26 Levosimendan Improves Renal Function in Patients with ADHF: Comparison with Dobutamine Yilmaz et al. Cardiovasc Drugs Ther 2007

27 Effects of levosimendan on ADCHF patients with renal impairment Rafouli-Stergiou P, Parissis J, et al. J Cardiovasc Med 2015

28 Treatment in CCU Levosimendan started No IV bolus Continuous IV infusion at 0.2 mcg/kg/min for the first 2 hours and then 0.1 mcg/kg/min for the next 22 hours

29 mm Hg L/min/m2 Improving status: CI and PCWP Cardiac index PCWP Time (h) after levosimendan

30 ml/h Improving status: urine output Time (h) after infusion

31 After 48h In-hospital improvement Swan-Ganz removed Discharge from CCU to ward After 5 days Hospital discharge Scheduled for ICD iv iron therapy Oral medications Digoxin mg QD Enalapril 5 mg q 12h Furosemide 80 mg q 12h Spironolactone 50 mg QD Bisoprolol 5 mg q 12h Warfarin 5 mg QD Injected iv iron at discharge Future evaluation for LVAD

32 Selecting the proper inotrope Pedersen and Felker. Crit Care Med 2008;36:106; Parissis and Mebazaa. Curr Opin Crit Care 2010;16:432 Patients with acute heart failure requiring inotropic therapy Increased pulmonary artery pressure Chronic betablockade Hypotension Acute cardiorenal dysfunction Ischemic heart disease Levosimendan Milrinone Levosimendan Milrinone Dobutamine Dopamine Norepinephrine Dopamine Levosimendan Dobutamine Levosimendan Dobutamine

33 Take home messages Peripheral hypoperfusion is often unrecognized and may be related with resistance to diuretic therapy. Renal function may deteriorate with use of IV diuretics alone. Early administration of inotropes when needed can prevent in-hospital deterioration and promote faster improvement.

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