Acute Decompensated Heart Failure : Optimizing Outcome

Dr Jaganmohan TharakanProfessor of CardiologySCTIMST, Trivandrum

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

ADHF

ResistantEndstage HF

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

Acute Decompensated Heart FailureOptimize 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

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)

650pts

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%

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

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

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

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%

biomarkers

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

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 therapyTransplant rejection, giant cell myocarditis, infiltrative process, active myocarditis with progressive ventricular dysfunction

Acute De-compensated HF: ManagementHypoxemia 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

Acute De-compensated HFDiuretic 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

Ultra filtration in ADHFCARESS 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

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

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

ADHF: Inotropic SupportIndications

• 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

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

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

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,

Vaso active drugs in ADHFRelaxin

• 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.

Vaso active drugs in ADHFRelaxin: 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

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

Vaso active drugs in ADHFUlaritide

• 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

Investigational drugs in ADHFAdenosine 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

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

ADHERE Registry: Mortality in ADHF : SBP and Ser Creatinine

Biomarkers in AHF

• To diagnose HF in ER• To predict outcome of HF therapy• To plan follow up strategy at discharge and

prognostication

Acute Heart FailureBiomarkers: 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

Biomarkers in HFBNP/ 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

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

Novel Cardiac Biomarkers in ADHF: contd.

• Midregion pro adrenomedullin• Galactin 3: indicator of myocardial collagen

deposition and fibrosis: marker of early HFWill a multi marker approach help in

prognostication of ADHF

Post ADHF discharge: Mortality 25% at 1 yearEVEREST trial

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 devicesUsefulness uncertain for mortality benefit

Heart Failure Risk ScoresCirc 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,

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′

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 reducedLVEF, 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.)

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

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

Thank You

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

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

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

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

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

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

Positive Inotropes in HFIndications

• 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

Old drugs: New dosage strategyDopamine 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

Diuretic Strategy in ADHFLow 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