Acute heart failure Spinar J. Brno, Czech republic Acute heart failure - definition Acute heart failure is: n Acute signs and symptoms of HF n Left ventricle dysfunctiuon (systolic and/or diastolic) n Urgent treatment needed Acute heart failure - definition De novo AHF Acute heart failure - clinics • Acute CHF decompensation without lung oedema or schock • Hypertension crisis with AHF • Lung oedema (saturation < 90%) • Cardiogenic schock (BPs < 90mmHg, CI < 0,5ml/kg/h, HR > 100) • AHF with high output (thyreotoxikósis, anemia, sepsis) • Right HF with low CI Acute heart failure - diagnosis Suspition for AHF (signs and symptoms) Acute heart failure - diagnostics ECHO – must be done n systolic function of LV n diastolic function of LV n regional wall motion n valves n pericardial fluid n infiltrativ process n hypertension crises - 50% normal systolic function (EF > 45%), intermittent diastolic dysfunction Acute heart failure - diagnostics BNP - doporučené pro dg n Increased in CHF n Increased in AHF n Normal value excludes AHF n Prognosis n Admition – discharge value n BNP > 500 pg/ml (100-500 ???) n Nt-proBNP > 1 800 pg/ml (300-1 800) Acute heart failure - diagnostics (Killip and Kimbal) Grade 1 n Wtihout HF Grade 2 n Light dyspnoe n Basal rales n Gallop n Lung congestionon chest X ray Grade 3 n Lung oedema Grade 4 n Cardiogenic schock – vasoconstrikction n - hypotension - oligouria X ray (Mezsaros) n CTR > 50% n Lung congestion 0 = fyziological finding I = hyeremia of upper lung II = intestitial lung oedema III = alveolar lung oedema Acute heart failure - epidemiology USA 1997 AHF AMI No hospitalisation 957 000 800 000 Hospit. mortality 10% 3% Rehospitalisation many few Guidelines for dg. 2004 1984 Guidelines for th. 2004 1984 No of random. studies 100 5 000 No of pts in studies 10 000 10 000 000 Acute heart failure - etiology CHF decompensation 65% Acute HF de novo 35% ACS (EKG, troponin) 30% Nieminen AHF registry EUROPE – ESC - 2005 ADHERE registry AHF 100 000 patients in USA • 48% patients with AHF had EF > 40% • 63% patients with EF > 40% were female • 2% patients had BPs < 90 mmHg • 48% patients had BPs 90-140 mmHg • 50% patients had BPs > 140 mmHg Heart Failure Hospitalizations: US AHF - prognosis Acute heart failure – prognosis Hospit. mortality 9% Discharge - 1. month 3% 1. – 3. month 3% 3. – 6. month 3% 6. – 12. month 3% 1 year mortality 21% Nieminen AHF registry - ESC 2005 Acute heart failure – conflicting information CHF decompensation 65% ACS (ECG, troponin) 30% EF > 40% 48% BPs > 140 mmHg 50% 1 year mortality 21 – 53 % Heart Failure Treatment Gaps n Heart failure affects at at least 10 million people in Europe and at least 4.9 million people in the US n Approximately 550 000 new cases are diagnosed each year in the US n Heart failure is a major and growing health care problem worldwide n There are currently no drugs that improve long-term survival in patients treated for heart failure n Current therapies provide short-term benefits but there are unmet needs for long-term outcomes Goals of AHF Management n Immediate – Improve symptoms and prevent morbidity and mortality – Restore oxygenation – Improve organ perfusion (kidney, brain, heart) – Treat volume overload n Intermediate – Stabilize patient and optimize treatment – Initiate maintenance regimen – Minimize ICU time – Minimize length of stay n Longer term disease management – Prevent early readmission – Improve long-term medical regimen, symptoms, and survival What Characteristics Would be Ideal in a Treatment for AHF? Characteristics of an Ideal Treatment for AHF n Offers early symptom relief n Promotes diuresis n Provides vasodilation (venous and arterial) n Improves end-organ function (eg, renal function) n Does not exacerbate arrhythmias n Does not exacerbate ischemia n Does not interfere with other AHF therapies (eg, b-blockers) n Decreases length of stay n Reduces hospitalizations and mortality Current IV Therapies for AHF Loop Diuretics n Mechanism of action – Inhibition of Na^+/K^+/2Cl^- symporter in the thick ascending limb of the Loop of Henle n Clinical Benefits – Rapid symptomatic improvement – Decreased volume overload n Clinical Drawbacks – Increased neurohormonal activation – Electrolyte disturbances and/or arrhythmias – Potentially worsened renal function Nitrovasodilators n Mechanism of action – cGMP-mediated venous and arterial vasodilation n Clinical Benefits – Reduce PCWP – Rapid symptomatic improvement n Clinical Drawbacks – Minimal indirect effect in increasing cardiac output – Hypotension, headache – Tolerance, tachyphylaxis (frequent titration) – Invasive monitoring – Rare cyanide toxicity (nitroprusside) Nesiritide Mechanism of Action n Recombinant human B-type natriuretic peptide (BNP) Nesiritide n Clinical Benefits – Rapid symptomatic improvement – Improvement in hemodynamic factors – No clinical evidence of tachyphylaxis n Clinical Drawbacks – Minimal indirect effect in increasing cardiac output – Incompatibilities; cannot be infused through same IV catheter as heparin (no heparin-coated catheters), insulin, bumetanide, enalaprilat, hydralazine, or furosemide – May cause hypotension – Associated with increased serum creatinine levels – Impact on hospitalization and mortality remains uncertain Effect of Nesiritide on Mortality Effect of Nesiritide on Mortality at 30 Days Effect of Nesiritide on Mortality at 180 Days Dobutamine Mechanism of Action Dobutamine n Clinical Benefits – Increased cardiac output and organ perfusion – Improves hemodynamics – Arteriolar and venous dilation – Slightly decreases preload and afterload n Clinical Drawbacks – Increased myocardial oxygen consumption – Tolerance over a period of days – Difficult to use with b-blockers – Increased arrhythmias – Possible or potential increased mortality Effect of Dobutamine on Survival Milrinone Mechanism of Action Milrinone n Clinical Benefits – Increased cardiac output and organ perfusion – Decreased PCWP – Decreased vascular resistance – Improvement of hemodynamic function – Left ventricular function improvement in ischemic heart disease n Clinical Drawbacks – Increased arrhythmias – Increased mortality with long-term use in patients with ischemic heart disease – Cannot be administered in same IV catheter as furosemide Effect of Milrinone on Survival Kaplan-Meier Survival Curves to 60 Days by Heart Failure Etiology and Treatment Assignment Levosimendan Levosimendan Early Clinical Development RUSSLAN Study Design RUSSLAN All-Cause Mortality LIDO Study Design LIDO All-Cause Mortality CASINO Study n Purpose was to test effects of levosimendan on long-term prognosis as compared with dobutamine and placebo n Patients with decompensated low-output chronic heart failure n Multicenter, randomized, double-blind, double-dummy, placebo-control, parallel-group trial n Primary end point was the composite of death or rehospitalization due to heart failure deterioration n Trial was stopped prematurely after 299 patients were enrolled because of a clear mortality benefit in favor of levosimendan CASINO Study Survival REVIVE II Study Design REVIVE II Primary End Point n Improved – If moderate or marked improvement in patient global assessment at each of 6 hours, 24 hours, and 5 days, and not worse at any time within 5 days n Worse – If died or experienced worsening or persistent CHF requiring a rescue therapy for heart failure at any time within 5 days – If at least moderate worsening in patient global assessment n Unchanged – If neither improved nor worsened Duration of Initial Hospitalization SURVIVE Study Design 180-Day All-Cause Mortality All-Cause Mortality in Patients With / Without Previous HF THANK YOU FOR YOUR ATTENTION