Acute Heart Failure in ICU2

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					  Broken Hearts
Acute Heart Failure




   Dr Andrew Turley
 Cardiology Consultant
      South Tees
     Overview: Acute Heart Failure
• New ESC guidelines
• Diagnosis
    – Serum natriuretic peptides
•   Non-invasive ventilation
•   Inotropes
•   Nesiritide
•   Cardiac Devices
     Overview: Acute Heart Failure
• New ESC guidelines
• Diagnosis
    – serum natriuretic peptides
•   Non-invasive ventilation
•   Inotropes
•   Nesiritide
•   Cardiac Devices
        Overview: Acute Heart Failure
• Complex syndrome caused by                    • The cardiac dysfunction may be
  impaired cardiac function                       related to
• 2 types:                                         – Ischaemia
    •   left ventricular systolic dysfunction      – Arrhythmias
        (LVSD)
                                                   – Valvular dysfunction
    •   Heart failure with preserved ejection
        fraction (HFPEF/HFNEF/Diastolic dys.)      – Pericardial disease
•   Commonest cause(s):                            – Increased filling pressures
    –   IHD, Hypertension, alcohol,                – Elevated systemic resistance.
        cytotoxics
• 30–40% of patients die within a
  year of diagnosis

• Around 900,000 people in the UK
    •   Expected to rise in the future
Drugs
                       Diagnosis
•   ECG
•   CXR
•   ABG
•   Laboratory Tests
    – A small elevation in
      cardiac troponin may
      be seen in patients
      with AHF without ACS.
• Echo
    Diagnosis: Cardiac Biomarkers
In patients with symptoms and signs of    • Natriuretic peptides
heart failure:                               – Negative predictive value
Measure serum natriuretic peptides           – There is no consensus
                                               regarding BNP or NT-proBNP
Refer to have echocardiography and             reference values in AHF.
specialist assessment within 2 weeks if      – Important prognostic
                                               information.
–Previous MI
    •BNP > 400 pg/ml or

    •NTproBNP > 2000 pg/ml




If BNP < 100 pg/ml or NTproBNP < 400
pg/ml, heart failure is unlikely in an
untreated patient
            Cardiac Biomarkers
Troponin/BNP/CRP
New Classification of MI-Type 2?
  Secondary to spasm,
   embolism, anaemia,     Acute MI
 arrhythmia, BP changes



      Type 1   Type 2     Type 3               Type 4             Type 5




                                     Type 4a            Type 4b
Troponinitis
Natriuretic Peptides: Origin and Stimulus of
                  Release




          Relaxation of smooth muscle cells
                                                                      NH 2N-
                                                                      NH         Ser
                                                                                                            ANP                                                H2N- Ser
                                                                                                                                                                 N-
                                                                                       Leu                                                                              Pro
                                                                                             Arg                                                                          Lys
                                                                                                                                   Gly Arg
                                                                                                Arg                          Gly             Met                             Met
                                                                                                      Ser              Phe                      Asp                                Val                    BNP

         Vasodilatation of veins and arteries
                                                                                                            Ser                                      Arg                                 Gin
                                                                                                                  Cys                                                                                                           Arg Lys
                                                                                                                                                                                            Gly                   Gly                     Met
                                                                                                                  S                                                                                                                          Asp
                                                                                                                  S                                      IIe                                   Ser             Phe
                                                                                                                                                                                                         Gly Cys
                                                                                                                  Cys                                Gly                                                                                          Arg



     GFR , Na+ reabsorption inhibited  diuresis
                                                                                                            Asn        Gly                         Ala                                                          S                                     IIe
                                                                                                   Ser                                                                                                          S
                                                                                                                             Leu             Gin
                                                                                                Phe                                Gly Ser                                                                  Cys                                   Ser
                                                                                          Arg
                                                                                                                                                                                                         Lys Gly
                                                                        COOH-       Tyr
                                                                                                                                                                                                   Val
                                                                                                                                                                                                                                                Ser
                                                                                                                                                                                                                          Leu             Ser


            SNS and RAS activity reduced
                                                                                                                                                                                             Leu                                Gly Ser
                                                                                                                                                                                       Arg
                                                                                                                                                                                 Arg
                                                                                                                                                                    HOOC-     His

                                                                              Arg Ser
                                                                  Ala
                                                                        Pro
                                                                                        Leu       Urodilatin
                                                                                           Arg
                                                                                                                                   Gly Arg                                H2N- Gly
                                                                Thr                           Arg                         Gly                Met                          H N-                       CNP
                                                                                                      Ser              Phe                     Asp                                 Leu
                                                                NH 2                                                                                                                                                            Leu Lys
                                                                NH                                          Ser                                                                              Ser                       Gly                Leu
                                                                                                                  Cys                                Arg                                                                                     Asp
                                                                                                                                                                                                   Lys              Phe

  ANP = Atrial Natriuretic Peptide                                                                             Cys
                                                                                                                   S
                                                                                                                   S


                                                                                                                                                     Gly
                                                                                                                                                         IIe                                             Gly
                                                                                                                                                                                                               Cys
                                                                                                                                                                                                                S
                                                                                                                                                                                                                                                 Arg

                                                                                                                                                                                                                                                      IIe

  BNP = B-type Natriuretic Peptide
                                                                                                                                                                                                                S
                                                                                                            Asn
                                                                                                                 Gly                    Ala
                                                                                                      Ser                                                                                    HOOC-             Cys                                Gly
                                                                                                Phe                      Leu         Gin
                                                                                                                             Gly Ser                                                                                Gly                         Ser

  CNP = C-type Natriuretic Peptide                                      HOOC-
                                                                        HOOC-       Tyr
                                                                                          Arg
                                                                                                                                                                                                                          Leu
                                                                                                                                                                                                                                Gly Ser
                                                                                                                                                                                                                                          Met




Adapted from Burnett JC, J Hypertens 2000;17(Suppl 1):S37-S43
     The natriuretic peptides: Biochemistry
                 of NT-proBNP
                                                                                                                                                 D R             I    S
                                                                                                                         90              M                                 S
                                                                                                                                     K                                         S
                                                                                                                                 R                                                 S
         1                                                                                                                       C
                                                                                                                                                                       G
   H2N— H
             P   L G                                                         proBNP                                                      F
                                                                                                                                             C                     C L
                                                                                                                                                                        100
                       S   P G                10                                                                                                                 C
                                 S   A                                                                                                       G                     K
                                          S             70                                                                           S                               V
                                                                                                    80                       G
                                                        Y                                                            Q                                                  L
                                                             T                                               V                                                                             R           108
                                                                 L                                  M                                                                                              R
                                                                     R            76           K
                                                                         A   P             P                                                                                                               H —COOH
                                                                                  R    S




                                                                             Cleavage
                                                                                                                                                                     D R       I       S
                                                                                                                                                             M                                 S
                                                                                                                                                         K                                         S
                                                                                                                                                     R                                                 S
                                              NT-proBNP                                                              BNP                             C
                                                                                                                                                             F
                                                                                                                                                                                                       G
     1                               10            70                        76
                                                                                                                                                                 C                     C L
                                                                                                                                                                               C
                                                                                                                                                                 G                     K
H2N— H   P   L G   S   P G   S   A   S             Y    T    L   R A     P   R —COOH                                                                     S                                     V
                                                                                                                                                 G
                                                                                                                                         Q                                                             L
                                                                                                                                 V                                                                           R
                                                                                                                         M                                                                                       R
                                                                                                                 K
         t½ 70-120 min                                                                                   P                                                                                                           H —COOH
                                                                                           H2N— S

                                                                                                                                         t½ 20 min
    Clinical Potential of BNP/NT-proBNP
• Extensively studied
    – A “blood test for heart failure”
•   Diagnosis-Raised in LVSD/AF/LVH/VHD/ACS
•   Screening for asymptomatic LVSD
•   Risk stratification & Prognosis in established HF
•   Therapy monitoring
•   Treatment of HF

    Normal BNP makes LVSD very unlikely
       NEGATIVE PREDICTIVE VALUE
     Overview: Acute Heart Failure
• New ESC guidelines
• Diagnosis
    – serum natriuretic peptides
•   Non-invasive ventilation
•   Inotropes
•   Nesiritide
•   Cardiac Devices
Acute Cardiogenic Pulmonary Oedema

                 • Common
                    – 15-20,000 hospital
                      admissions per annum in
                      UK


                 • Deadly
                    – 15-20% in-hospital
                      mortality


                 • Costly
                    – 6.5 million hospital days
                      per annum in USA
Initial Treatment
             • The evidence in
               favour of morphine
               use for AHF is limited.

             • Multiple agents are
               used to manage AHF,
               but there is a paucity of
               clinical trials data and
               their use is largely
               empiric.

             • Most agents improve
               haemodynamics but no
               agent has been shown
               to reduce mortality.
    Non-invasive Ventilation In Acute Cardiogenic
                Pulmonary Oedema




“When the household vacuum cleaner is employed, the machine should be run for some
                       minutes first of all to get rid of dust”

Poulton EP, Oxon DM: Left-sided heart failure with pulmonary oedema: Its treatment with
          the "pulmonary plus pressure machine." Lancet (1936);231:981-983.
Physiological Improvement with CPAP in Patients
                   with ACPO




         Reduced acidosis, respiratory rate and heart rate


                                     Kelly et al. Eur Heart J 2002;23:1379-1386
Mortality Benefit of CPAP/NIPPV in Patients with
                      ACPO

                                   Mortality reduced
                                   from 22% to 11%

                                       RR 0.53
                                   (95% CI 0.35-0.81)

                                   (Individual Group
                                      Sizes small)
                                     However, in 3CPO,
                                     a large RCT........

                            Masip et al. JAMA 2005;294:3124-3130
3CPO                       Trial summary

 Background                             Intervention
 Aims                                   • Randomised (1:1:1)
                                            – Standard oxygen therapy (by
 • Clinical effectiveness of non-             facial mask)
   invasive ventilation
                                            – CPAP (5 cmH2O up titrated to
 • Comparative effectiveness of               a maximum of 15 cmH2O)
   CPAP and NIPPV
                                            – NIPPV (8/4 cmH2O up titrated
 • Safety of non-invasive ventilation         to a maximum of 20/10
                                              cmH2O)

 Hypothesis:                            • Inhaled oxygen of 60%
                                        • Attending physicians were
                                          encouraged to use vasodilator
 • Non-invasive ventilation reduces       (nitrate) and diuretic therapy
   mortality                            • Opiate therapy was administered
                                          at the discretion of the treating
                                          physician
3CPO             Outcome: Any NIV v Standard
                         Mortality

              Standard           Non-         Odds Ratio         95%         P Value
              Therapy          Invasive                       Confidence
                              Ventilation                      Intervals


 7-Day          9.8%             9.5%             0.97        0.63 to 1.48    0.869


 30-Day         16.7%           15.4%             0.93        0.65 to 1.32    0.685


 Active Trial 1069 patients ~ 350 per arm
 Baseline Characteristics matched
 Baseline Medications matched
 Baseline Interventions matched (nitrate, diuretic, opiate, oxygen)
 3CPO
                             Outcome: Hospital stay

                                      Standard   CPAP       NIPPV      P-value



    Admitted to intensive             8.8%       9.1%       6.6%       0.411
    Care
    Admitted to high-                 7.7%       10.3%      10.9%      0.301
    dependency Care
    Admitted to coronary              38.1%      43.7%      40.9%      0.337
    Care
    Median length of hospital         8 (5-13)   9 (5-16)   9 (5-16)   0.313
    stay in days ( IQR)




No significant differences (P>0.05)
3CPO
                       CONCLUSIONS
 • In patients with acute cardiogenic pulmonary
   oedema non-invasive ventilation (1069 patients)
    – UK study, RCT:

   Produces more rapid resolution of metabolic abnormalities
                   and respiratory distress

         Has no major effect on 7-day or 30-day mortality

 Is beneficial irrespective of the mode (CPAP or NIPPV) of delivery
     Overview: Acute Heart Failure
• New ESC guidelines
• Diagnosis
    – serum natriuretic peptides
•   Non-invasive ventilation
•   Inotropes
•   Nesiritide
•   Cardiac Devices
                        Inotropes
• Inotropic agents should only    • Dobutamine
  be administered in patients          – Positive inotropic agent
  with low SBP or a low                  acting through
  measured cardiac index in the          stimulation β1-receptors
  presence of signs of                   to produce dose-
  hypoperfusion or congestion.           dependent positive
                                         inotropic and
                                         chronotropic effects.
                                       – The infusion rate may be
                                         progressively modified
                                         according to symptoms,
                                         diuretic response.

                                  •   The elimination of the drug is rapid
                                      after cessation of infusion.
                                  •   Care should be exercised in weaning
                                      patients from dobutamine infusion.
        Treatment related to BP




Respiratory support, Furosemide (infusion)
   IV Dobutamine plus low dose IV GTN
                 ± IABP
         Other treatment options
• Vasopressin antagonists     • Levosimendan infusion
   – Unproven                   increases cardiac output
                                and stroke volume and
                                reduces pulmonary wedge
• Levosimendan is a calcium     pressure, systemic vascular
  sensitiser that improves      resistance, and pulmonary
  cardiac contractility         vascular resistance.

• Exerts significant          • Vasopressors
  vasodilatation mediated       (norepinephrine) are not
  through ATP-sensitive         recommended as first-line
  potassium channels            agents
     Overview: Acute Heart Failure
• New ESC guidelines
• Diagnosis
    – serum natriuretic peptides
•   Non-invasive ventilation
•   Inotropes
•   Nesiritide
•   Cardiac Devices
                 Vasodilators
• Vasodilators relieve pulmonary congestion usually
  without compromising stroke volume or increasing
  myocardial oxygen demand in acute HF.
• Often combined with diuretic ± inotrope
• Nitrates: Predominantly venodilator effect.
                          Nesiritide
• Intravenous                         • Non-invasive BP
• Recombinant form of                   measurements are
  human B-type                          usually adequate.
  natriuretic peptide,
• Venous and arterial                 • Combination with
  vasodilator with a                    other i.v. vasodilators
  combined modest                       is not recommended.
  diuretic and natriuretic            • 2005
  effect.
                                           – 2 meta-analysis
• Approved by FDA in 2001
                                             ? Renal safety
   – Reduce PCWP (@ 3 hrs!)

         Nesiritide is not available in most European countries.
     Ascend HF*: AHA 14th Nov 2010
                                               • 7141 patients
                                               • 1:1
                                                    – Placebo vs Nesiritide




              Safe
      No mortality benefit
Minimal symptomatic improvement

*Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial
     Overview: Acute Heart Failure
• New ESC guidelines
• Diagnosis
    – serum natriuretic peptides
•   Non-invasive ventilation
•   Inotropes
•   Nesiritide
•   Cardiac Devices
What is the rhythm?
Causes of death in heart failure
  NYHA II         NYHA III             NYHA IV

        12%
                       26%           33%
                                             56%
          24%   59%

64%                      15%         11%



Pump failure
                               I       No Limitation
Other                          II      SOB on severe exertion
                               III     SOB on mild exertion
                               IV      House bound (SOB at rest)
Sudden death
           Pre-implant counselling
           How do you want to die?
Heart failure death        Sudden death
           Device X Rays
ICD Lead          BiV LV Lead position
ICD Myths
      • Myths
         – ICDs prevent syncope
         – Contacts can be electrocuted
           by ICD discharge
         – Not safe to use mobile phone,
           mircowave, playstation etc.
         – Will stop you dying from VF
      • “Diathermy kills patients &
        devices”
         – PPM – may inhibit (pulse
           oximetry)
         – ICD – will detect as VF
           (reprogram)
 Consequences of tachycardia therapy

VT Storm               Inappropriate shocks
         End of life issues: NECVN




Ventricular arrhythmias and/or poor LV function → is an ICD indicated ?
                Temporarily disabled with a ring magnet
The Future?
       Intrathoracic Impedance: Concept
                  The Reality




Drier lungs              Wetter lungs
means the       Less     means the       More
intrathoracic   Fluid    intrathoracic   Fluid
impedance is             impedance is
higher                   lower
                       Summary
• Normal BNP makes LVSD very unlikely
   – NEGATIVE PREDICTIVE VALUE
• Non invasive ventilation
   – Produces more rapid resolution of metabolic abnormalities and
     respiratory distress
   – Has no major effect on 7-day or 30-day mortality
   – Is beneficial irrespective of the mode (CPAP/NIPPV)
• Respiratory support, Furosemide (infusion), IV Dobutamine
  plus low dose IV GTN, (± IABP)
• Nesiritide
   – Safe, No mortality benefit, Minimal symptomatic improvement
• ICD: Temporarily disabled with a ring magnet
• End of life issues: NECVN

				
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