2013 sept 20_final__acute_decompensated_heart_failure

1. Acute Decompensated Heart
Failure : Optimizing Outcome
Dr Jaganmohan Tharakan
Professor of Cardiology
SCTIMST, Trivandrum

2. Acute Decompensated Heart
Failure
• Syndrome complex characterized by rapidly
developing symptoms of new onset de novo heart
failure or worsening of chronic heart failure
culminating in acute decompensation and
requiring monitored therapy including
hospitalization
• Sentinel prognostic event with 50% risk of
rehospitalization at 6 months and 30% mortality at
1 year

3. ADHF
Resistant
Endstage HF

4. Acute Heart Failure
• >80% have decompensation of existing HF
• Often several days of gradual weight gain and
worsening dyspnoea precede ADHF
• Fluid overloading is the acute presentation
• Close to 50% have HF and preserved EF
• Cardiogenic shock is a rare presentation
• ACS and renal dysfunction to be assessed
early

5. Acute Decompensated Heart Failure
Optimize Outcome: Opportunities
• Recognition of AHF and instituting prompt life saving
intervention: time saved is life saved
• Aggressive intervention to support circulation when a
treatable/ reversible cause is identified: especially in
De novo AHF
• Optimize disease modifying medications/ interventions
once stabilized
• Prognostic markers/ risk score for intense out of
hospital monitoring
• At hospital discharge: Guideline directed medical
therapy as re-hospitalization for AHF is 50% at 6
months

6. ADHF: Reversible/ Treatable causes
• Non adherence to medications, salt/ fluid restriction
• Acute myocardial ischemia/ACS
• Hypertension
• AF/ tachy/ brady arrhythmias
• Negative inotropic drugs/ NSAIDS/ Steroids/
thiazolidinediones
• Alcohol/ cocaine
• Endocrine disorders( DM, thyroid)
• Infections/ anaemia/renal dysfunction/
• Other CV disorders(IE/ valve disease)

7. 650

8. Acute heart Failure
( TVM HF Registry 624 pts)
• Mean Age 60 years
• Acute de novo HF 40%
• Males 69%
• IHD 69.5%
• DCM 14.5%
• RHD 8%
• Diastolic HF 3%
• HT55%, DM 52%, Smoking 44%, AF 14%, CKD
15%
• In hospital mortality 9%

9. ADHF pts characteristics
(OPTIMISE registry)
• Preserved LV function
• EF 55%
• Age 75yrs
• Males 38%
• IHD 38%
• BNP 601pg/ml
• Reduced LV function
• EF 24%
• Age 70 yrs
• Male 62%
• IHD 55%
• BNP 1170 pg/ml

10. General Concepts in management of
ADHF
• 1. Severity of ADHF presentation does not
always predict long term outcome
• 2. LVEF at presentation and improvement/
worsening influence outcome
• 3. Hemodynamic improvement should come
from amelioration of myocardial dysfunction
rather than by increasing contractility with
inotropes

11. General Concepts in management of
ADHF
• 4. Ischemic Viable myocardium requires
revascularization
• 5. Attempt to limit myocardial and renal
damage: intervention to improve clinical signs
and symptoms like diuretics, vasodilators,
inotropes may worsen myocardial and renal
damage

12. Clinical Scenario at presentation
• High SBP > 160 mmHg 25%
• Normal to High normal BP 50%
• Hypotension (SBP<90) 10%
• Cardiogenic shock 1%
• Flash pulmonary edema 3%

14. biomarkers

15. ADHF: Noninvasive Investigations
• Chest X ray, ECG
• 2D Echo Doppler: EF, LV dimension, wall
thickness, wall motion, valve function, PAH,
RV function
• Myo. Viability/ reversible ischemia study if
CAD suspected and suitable for
revascularization
• CMRI for myocardial infiltration/ fibrosis/ scar

16. ADHF: Invasive Investigations
• PA catheterization: hypoperfusion with uncertain
volume status/respiratory disease
• CAD suspected and eligible for revascularization
• Endo myocardial Biopsy when specific diagnosis
suspected & can alter therapy
Transplant rejection, giant cell myocarditis,
infiltrative process, active myocarditis with
progressive ventricular dysfunction

17. Acute De-compensated HF: Management
Hypoxemia and respiratory failure due to pulmonary
Edema
• Usual treatment for acute pulmonary edema
• O2 by mask : O2 sat>= 90%/
– Noninvasive ventilation CPAP, NIPPV (avoid if
hypotension/altered sensorium)
– Intubated ventilation
• Vasodilators if SBP >110mmHg
– NTG
– Nitroprusside
– Nesiritide

18. Acute De-compensated HF
Diuretic Therapy
• Bolus parenteral Loop diuretics: equal to pt’s
oral maintenance dose: Infusion / intermittent
bolus/ high dose diuretics
• Add another diuretic like thiazide group/
metolazone
• Add small dose dobutamine at 2-5 mic/kg/m
• Resistant fluid overload: Ultra filtration
• Aquaretics if euvolumic hyponatremia

19. Ultra filtration in ADHF
CARESS trial(188 pts)
• In patients with volume overload ADHF as it
reduces volume and electrolytes equally
• UNLOAD(200 pts): superior to diuretics
• CARESS study:High risk ADHF pts.: Similar
outcome for weight reduction, but higher rise
in ser creatinine, need for dialysis, and other
adverse events.
• AVOID HF: Ongoing trial

20. Inotropes in Heart failure
Inotropes/ Vasopressors/ both
• Inotrope: Dobutamine: minimal vasodilatory
effect (beta 2 stimulation)
• Inotrope with vaso dilatation: Milrinone,
Levosimendan
• Vasopressor with Inotropic action: Dopamine,
Nor epinephrine

21. Pts with hypotension/ Hypo-
perfusion
SBP <85 mmHg/ reduced urine output/ lactate
• Exclude hypovolumia
• Modify dose of ACEI/ beta blockers
• Dobutamine infusion
• Short term circulatory support
• I/V levosimendan if exposed to beta blockers
• Vasopressor like dopamine/ norepinephrine if in
cardiogenic shock despite an inotrope, to maintain
SBP and end organ perfusion

22. ADHF: Inotropic Support
Indications
• Until definitive therapy( MCS/transplant) or
resolution of precipitating cause in Pts with
cardiogenic shock , to maintain systemic
perfusion and preserve end organ function
• Short term inotropic support in pts with
severe systolic LV dysfunction, low BP, low
CO : to preserve end organ function
• Long term palliation with inotropic support

23. Mechanical Circulatory Support
• MCS for resistant HF: definitive management
( transplant) or recovery anticipated.
• Percutaneous/ extra corporeal assist devices:
bridge to recovery/ bridge to decision when in
acute profound hypotension

24. Pts with AF and fast VR
• Anticoagulation with heparin
• Rhythm control:
– Emergent DC cardioversion if hemodynamically
unstable
-- Elective DC cardioversion if recent AF(<48hrs) or
TEE echo excludes LA thrombus
• Rate control: Digoxin, ? amiodarone

26. Potential New Therapies
• Cinaciguat: Soluble Guanilate cyclase activators
• Chimeric natriuretic peptides: Avoids arterodilating
hypotensive effects of BNP, with venodilating and
natriuretic action intact
• Istaroxime: membrane Na+ K+ ATPase inhibitor with
SERCA2a activation.
• Stresscopin: Human peptide Urocortin2: Activates
myocardial reperfusion injury protection pathways:
increase EF and CO, decrease SVR,

27. Vaso active drugs in ADHF
Relaxin
• Endogenous peptide associated with
pregnancy and acts through relaxin receptor:
reduce inflammation, decrease fibrosis,
increase vasodilation, promote renal blood
flow, increase vascular endothelial growth
factor, and angiogenesis.

28. Vaso active drugs in ADHF
Relaxin: Serelaxin
• RELAX HF:1161 pt. of ADHF with preserved SBP >115
mmHg.
• Serelaxin 30 ug/kg/day x48 hrs vs Placebo
• Significant improvement in dyspnoea scale
• No impact on short term mortality/ HF readmission
at 60 days, though 180 day mortality was
significantly lower.
• Hypotensive episodes higher but renal dysfunction
less than placebe group

29. Investigational drugs in ADHF
Omecamptive Mecabril
• First selective cardiac Myosin activator: acts
through greater binding of myosin to actin:
– Increases myo. contractility without increase in O2
consumption: increased EF, stroke volume,
decreased LVES and LVED volume
– Chest pain, tachycardia and myo. Ischemia more
common
ATOMIC- AHF study is Phase 3 trial: ongoing

30. Vaso active drugs in ADHF
Ularitide
• Synthetic form of Urodilantin: human natriuretic
peptide produced in kidney: induces natriuresis and
diuresis. Also potent vasodilator( increases
intracellular cyclic GMP) and increased renal blood
flow) : Two double blind studies have shown
favorable outcome in ADHF by symptom
improvement and hemodynamics
• Phase 3 trial(TRUE-AHF >2110 pts) ongoing

31. Investigational drugs in ADHF
Adenosine A1 receptor antagonist:
Rolophylline
• Preserve GFR, improve diuresis, increase
sodium excretion by kidney
• Phase 2 trial: better relief of dyspnoea and
lesser renal dysfunction
• Phase 3 trial: PROTEC:2033 pts.: negative trial
with none of the primary end points
significant and safety was questioned due to
neurological side effects: seizure and stroke

32. Newer Molecules in treatment of
AHF
• Overall impact in treatment is small
• Mechanical Circulatory support will continue
to be used more frequently to bridge to
recovery/ transplant/ destination therapy
• Newer strategies will be required, for any
major impact in management of AHF

33. ADHERE Registry: Mortality in ADHF :
SBP and Ser Creatinine

34. Biomarkers in AHF
• To diagnose HF in ER
• To predict outcome of HF therapy
• To plan follow up strategy at discharge and
prognostication

35. Acute Heart Failure
Biomarkers: BNP
• BNP/ NT pro BNP : to support clinical judgement for
diagnosis of ADHF
• BNP/ NT pro BNP and/or cardiac troponins in
establishig diagnosis severity and prognosis of ADHF
• BNP/ NT pro BNP to guide therapy in ADHF
• Other biomarkers of myocardial injury/ fibrosis: ST2

36. Biomarkers in HF
BNP/ NT pro BNP
• PROTECT (150 pts): Compensated CHF
• HOME HF outpatient monitoring
evaluation(350 pt.)ADHF pts: BNP based home
management vs BNP blinded (use wt/
symptoms/signs) vs Controls (usual care)
• GUID-IT: ADHF pts monitored with NT pro
BNP guided therapy

37. Novel Cardiac Biomarkers in ADHF
• Soluble ST2 receptor: interleukin family: upregulated
by myocardial strech: predicts 1 year mortality
• NGAL: neutrophil gelatinase ass. Lipocalin: marker of
kidney injury: higher levels predict 30 day mortality
• Copeptin: C terminal protein of pre pro vasopressin:
highest quartile predicted very high 90 day mortality

38. Novel Cardiac Biomarkers in ADHF:
contd.
• Midregion pro adrenomedullin
• Galactin 3: indicator of myocardial collagen
deposition and fibrosis: marker of early HF
Will a multi marker approach help in
prognostication of ADHF

39. Post ADHF discharge: Mortality 25% at 1 year
EVEREST trial

40. HF: Monitoring to predict/ prevent
ADHF admissions
• Devices: Externally applied Impedance
Cardiography (PREDICT study 211 pts)
• Internally placed devices measuring intra
thoracic impedance(PARTNER 2HF: CRT device
with Impedance monitoring): predicted
subsequent admission for ADHF
• PA / LA/ LVEDP monitoring devices
Usefulness uncertain for mortality benefit

41. Heart Failure Risk Scores
Circ HF 2013
End point: Death/ transplant/ Assist device
• Heart Failure Survival Score(200pts):
– IHD, QRS>120ms, LVEF, Resting HR, mean BP, O2
consumption, ser Na
• Seattle Heart Failure model: (1100pts)
– Age, LVEF, NYHA class, SBP, Diuretic dose, Na+,
uric acid, ser. Chol., lymph. count
- Sex, IHD, QRS >120ms, ICD, CRT, betablockers,
ACEI, Statins, Allopurinol,

42. Heart Failure Risk Scores
• SHOCKED predictor: (900pts):
Age>75, NYHA>II, AF, COPD, CKD, LVEF<20%, DM
• PACE: (900 pts) PVD, Age >70, Creatinine >2,
EF < 20%,
• ADHERE registry( for acute mortality): SBP, Ser
creatinine and BUN
• Frankenstein: BNP , 6 WT′

43. In multivariable models, nearly all tested covariates performed similarly across LVEF
strata for the outcome of death from any cause, as well as for HF-related and all-
cause hospitalizations.
Conclusions—We found that in a large, diverse contemporary HF population, risk
assessment was strikingly similar across all LVEF categories. These data suggest that,
although many HF therapies are uniquely applied to patients with reduced
LVEF, individual prognostic factor performance does not seem to be significantly
related to level of left ventricular systolic function. (Circ Heart Fail. 2013;6:635-646.)

44. Post Discharge Multi disciplinary
Management Program
• Cardiac Rehabilitation: periodic follow up,
education, optimize drug treatment, general
medical care, exercise program, ensure access to
hospital care
• Palliative Care: frequent hospitalization, not
listed fro transplant or mechanical circulatory
support, poor quality of life, dependence for daily
needs, close to end of life
• Heart failure team: practitioner, nurse,
pharmacist, dietician, psychologist,
physiotherapist

45. Conclusion
• Acute Heart Failure, is a medical emergency
and rapid, coordinated multi disciplinary
approach can significantly reduce mortality.
• Stabilized patients of AHF, to have GDMT/
devices/ revascularization as indicated
• At discharge: patient education, counseling,
compliance with GDMT and frequent clinic
visits can prevent re-hospitalization for AHF

46. Thank You

47. I/V Vasodilators in AHF
• Nitroglycerine: 10 – 100 ugm/min
• Nitroprusside: 0.03 to 0.3 mic/kg/min
• Nesiritide: 0.1 mic/kg/min

48. General Concepts in management of
ADHF
• 1. AHF with preserved EF is being recognized
more often and carry similar long term prognosis
• 2. Severity of ADHF presentation does not always
predict long term outcome
• 3. LVEF at presentation and improvement/
worsening influence outcome
• 4. Hemodynamic improvement should come
from amelioration of myocardial dysfunction
rather than by increasing contractility with
inotropes

49. General Concepts in management of
ADHF
• 5. Ischemic Viable myocardium requires
revascularization
• 6. Attempt to limit myocardial and renal
damage: intervention to improve clinical signs
and symptoms like diuretics, vasodilators,
inotropes may worsen myocardial and renal
damage

50. Risk Score to Predict Acute
Decompensated HF: PRIDE Score
• Elevated NT Pro BNP>450 pg/ml(<50yrs) 4
• Interstitial pulm edema
2
• Orthopnea 2
• Lack of fever(r/o infection) 2
• Current diuretic use/Age>75/ rales on lung exam/
lack of cough 1
• Early identification and institution of treatment/
correction of causative factors improve outcome

51. European Heart failure Study
• Worsening of chronic HF: 65%
• Acute pulmonary edema: 16%
• Hypertensive HF: 11%
• Cardiogenic shock: 4%
• Acute right heart failure: 4%
ACS presenting as HF :10% of all ACS

52. ADHF: Prognostic markers
• Mathematical model using NT pro BNP value as a
continuous variable with age and pretest probability
of HF had 96% sensitivity and 84% specificity for
predicting a ADHF
• Mid regional pro ANP >120pmol/l: also affected by
age, ender, BMI, AF,renal function

53. Positive Inotropes in HF
Indications
• Advaced HF,
• Reduced EF, LV dilatation,
• Euvolumic hypotensive ( adequate filling
pressure)
• Intolerant to vaso dilators
• Signs of diminished peripheral perfusion or
renal other end organ dysfunction

54. Old drugs: New dosage strategy
Dopamine and furosemide
• Low dose dopamine 5 mic/kg/min and low
dose furosemide appears safer for renal
fuction deterioration (DAD HF study)
• Phase 3 trials ongoing : DAD HF 2, ROSE AHF

55. Diuretic Strategy in ADHF
Low vs high dose furosemide:
DOSE trial(308pts)
• Low( usual Furosemide dose)vs High(2.5 times) X
continuous vs intermittent parenteral dosing
• No significant difference in safety/ efficacy
• Acutely, high dose group had higher creatinine
elevation, but at 7 days, this was not significant
• Secondary end points: greater dyspnoea relief, fluid
loss and weight loss with higher dose