Οξεια καρδιακη ανεπαρκεια με υποταση Γεώργιος Μπακώσης Τμήμα Καρδιακής Ανεπάρκειας, Β’ Παν/κή Καρδιολογική κλινική, Π.Γ.Ν. “ΑΤΤΙΚΟΝ”

Disclosures I have no actual or potential conflict of interest in relation to this presentation

What is the preferable IV therapy of Hypotensive AHF according to the ESC guidelines ? 1. iv diuretics 2. iv nitrates 3. iv inotropes 4. 1 and 2 5. 1 and 3

Patient profile Demographics and risk factors 65 year-old male Admitted April 2017

Patient profile Cardiovascular history First Heart Failure diagnosis in 2015 - Acute anterior MI PCI in LAD in 2015 Negative SPECT for ischemia one year after PCI NYHA II, 2015 Mild renal failure Creatinine 1.6 mg/dL (NR 0.6-1.2) - eGFR 46 ml/min/1,73m2 Chronic anemia Haemoglobin 10.7 g/dL (NR 13.5-17.5) Hospitalized for decompensation in January 2017

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 per os Eplerenone 50 mg Bisoprolol 2.5 mg Acetylsalicylic acid 100 mg Atorvastatin 20 mg Warfarin (episodes of AF)

Clinical evaluation at outpatient clinic (referral) Early April (10 wks after last hospitalisation) Decreased exercise tolerance (NYHA III) Increased furosemide 80  160 mg/day Evaluated for ICD

ER evaluation - NYHA IV Next two weeks (mid April) Symptom worsening Progressive dyspnoea Weight gain 5 kg ER admission NYHA IV 23 April 2017

ER Physical exam results General Dyspnoea at rest Vital signs BP 90/60 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 +

ECG

Admission echocardiogram Left Atrium: 61 mm (NR, 20 – 40) LVEDD: 76 mm (NR, 35 – 56) LVESD: 66 mm (NR, 25 – 40) LVEF, Simpson: 28% (NR > 55 %) Long axis Systole RV LV AV Mitral insufficiency 2+/4 Aortic insufficiency 1+/4 Tricuspid insufficiency 2+/4 LA MV Elevatet right heart pressures (estimated pulmonary pressure = 48 mmHg)

Admission laboratory tests Haemoglobin 10.4 g/dL (NR= 13.5-17.5) Urea 165 mg/dL (NR= 10-20 mg/dL) Creatinine 2.3 mg/dL (NR= 0.6-1.2 mg/dL) Sodium 131 mEq/L (NR= 136-145 mEq/L) Potassium 3.54 mEq/L (NR= 3.5-5.0 mEq/L) NT-proBNP 6550 pg/ml (NR <300pg/ml) INR 2.7 (NR= 2.0-3.0) Arterial blood gas pH = 7.39 (NR = 7.35-7.45) PO2 = 67 mm Hg (NR=80-100 mm Hg) PCO2 = 39 mm Hg (NR=35-45 mmHg) HCO3- = 25 mEq/L (NR=21-28 mEq/L)

Case summary History Presentation 65 year-old male 2-year known history of HF due to ischemic cardiomyopathy Presentation Worsening HF in the last 2 weeks  NYHA IV SBP: 90 mmHg Acutely aggravated renal dysfunction Pulmonary and systemic congestion Mild chronic anaemia

Eur Heart J 2016;37:2129-2200

What is the preferable IV therapy of Hypotensive AHF according to the ESC guidelines ? 1. iv diuretics 2. iv nitrates 3. iv inotropes 4. 1 and 2 5. 1 and 3

Eur Heart J 2016;37:2129-2200

Initial treatment Admission to the ward 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 discontinued

ACEi and b-blockers in AHF ACEi should be stopped if: Potasium rises to >5.5 mmol/L or Creatinine >100% or >3.5 mg/dL (eGFR=20mg/min/1.73m2) B-blockers If increasing congestion, increase dose of diuretic or halve dose of beta-blocker (if increasing diuretic dose does not work) Both should be stopped in hypotension ESC Guidelines 2016

Evolution in ward NEXT STEP After 2 hours No significant improvement Worsening dyspnoea (oxygen saturation 89%) Rales over 2/3 of lungs Blood pressure: 90/60 mm Hg Decreased urine output NEXT STEP

What is the next step ? 1. iv nitrates 2. iv dobutamine 3. iv levosimendan 4. iv norepinephrine

INOTROPIC SUPPORT Dobutamine started Continuous IV infusion at 3-5 μcg/kg/min for the next 48 hours ECG monitoring

Improving status: urine output

In-hospital improvement After 48 hours Clinical improvement Blood pressure 90/55 mmHg HR: 96/min Hypotensive episode during the initiation of bisoprolol Ivabradine initiated at 2,5 mg x 2 and uptitrated to 5 mg x 2 in the next 3 days

Elevated HR at discharge is a predictor of one year mortality in HF patients (OFICA) Importance of controlling HR early in the post-discharge management of HF patients Logeart et al. Eur Heart J 2012

Pre-discharge and discharge management At 7th day Hospital discharge, NYHA II HR: 72 bpm NT-proBNP reduction >30% On oral medication >24h Follow-up in 2 weeks Evaluataion for comorbidities Scheduled for ICD Future evaluation for LVAD Oral medications at discharge Ivabradine 5 mg x 2 Furosemide 80 mg Eplerenone 50 mg Warfarin Atorvastatin 20mg

TAKE HOME MESSAGES Central hemodynamics, SBP, HR and volume status guide the optimal early phase management of AHF. Close monitoring and re-evaluation of therapy may be needed, especially if congestion/hypoperfusion persists Chronic life saving medications in appropriate combinations should be initiated and up-titrated after clinical stabilization. A detailed post-discharge plan with an early follow-up visit (2 weeks in high risk patients) along with evaluation for specific HF therapies (eg. ICD, CRT, VAD), management of comorbid conditions and patient education is mandatory.

Criteria for ICU/CCU admission Need for intubation Signs/symptoms of hypoperfusion SaO2 <90% (despite supplemental O2) RR > 25/min, use of accessory muscles SBP <90 mmHg, 40 > HR > 130 bpm

IV loop diuretics: Bolus vs. continuous infusion Metanalysis: Continuous Infusion Superior to Bolus Injection: Total Urine output P = 0.003 Increase in s. Creatinine P < 0.00001 Length of Hospitalization All Cause Mortality P = 0.00005 Salvador DRK et al. The Cochrane Database of Systematic Reviews 2005

IV loop diuretics in AHF DOSE trial No difference in death, rehospitalization or RF visits at 60d Felker et al, N Engl J Med 2011

MRAs in AHF MRA should be stopped if: Potasium rises >6.0 mmol/L or Creatinine >3.5 mg/dL Hypotension ESC Guidelines 2016

B-blockers in AHF: B-CONVINCED Similar patient improvement (Green: keep BB – Red: stop BB) Similar outcome Higher use of BB at 3 months Jondeau et al. Eur Heart J 2009

Parissis & Mebazaa. Curr Opin Crit Care 2010

Levosimendan improves renal function in ADHF: Comparison with Dobutamine Yilmaz et al. Cardiovasc Drugs Ther 2007

Impact of Discharge Use of Beta Blocker on Early Clinical Outcomes in Heart Failure 30 day Survival P<0.01 1.00 P=0.0003 0.95 0.90 Survival Probability 0.85 0.80 0.75 Beta-Blocker No Beta-Blocker 0.70 10 20 30 40 50 60 70 80 90 100 110 120 130 Patients at Risk Beta-blocker 1,946 1,855 1,649 333 68 No Beta-blocker 362 337 304 60 7 Days After Hospital Discharge *Only subset of patients with 60- to 90-day follow-up are included. Patients with beta-blocker contraindications are excluded. 27 Fonarow et al. J Am Coll Cardiol. 2008;52:190-199. 36

Implantable device diagnostics on day of discharge identify heart failure patients at increased risk for early readmission for heart failure Four diagnostic criteria were evaluated on the discharge day: (i) intrathoracic impedance >8 Ω below reference impedance (ii) AF burden >6 h (iii) CRT pacing <90% and (iv) heart rate >80 b.p.m. Patients were considered to have higher risk for HFR if ≥2 criteria were met, average risk if 1 criterion was met, and lower risk if no criteria were met. Small et al, Eur J Heart Fail 2014

Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced LVEF (ETHIC-AHF): A randomised study The early co-administration of ivabradine and beta-blockers during hospital admission for acute HFrEF is feasible and safe, and it produces a significant decrease in HR at 28 days and at four months after hospital discharge. It also seemed to improve systolic function and functional and clinical parameters of HF patients at short-term. Hidalgo et al, Int J Cardiol 2016

Int J Cardiol 2015;201:231-236