BART COX, M.D., FACCDIRECTOR, ADVANCED HEART FAILURE PROGRAMASSOCIATE PROFESSOR OF MEDICINEUNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE

NONE

A complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood

HF with LVEF < 40%

HF with LVEF > 50%

HF with LVEF 41-49%

HFpEF + LVEF previously < 40% that is now > 40%

NYHA I: Ordinary physical activity does not cause symptoms of HF

NYHA II: Ordinary physical activity results in symptoms of HF

NYHA III: Less than ordinary physical activity results in symptoms of HF

NYHA IV: Unable to carry on any physical activity without HF symptoms, or symptoms of HF at rest

A: High risk for HF but without structural heart disease or HF symptoms (e.g., DM, metabolic syndrome, CAD, obesity, hypertension, history of familial CM, or use of cardiotoxin)

B: Structural heart disease but without history of HF signs or symptoms (e.g., asymptomatic valve disease, LVH, reduced LVEF, MI)

C: Structural heart disease + prior / current HF symptoms or signs

D: Advanced HF: Refractory HF requiring specialized interventions (e.g., transplant, MCS, etc)

LVEF < 40% with NO history of signs and symptoms of HF

If there is ANY history of signs and symptoms of HF, this is NOT asymptomatic LV dysfunction. Must call it HF +NYHA class NYHA I: no symptoms currently with ordinary

activity NYHA II: symptoms of HF with ordinary activity NYHA III: symptoms of HF with less than ordinary

activity NYHA IV: symptoms of HF with any activity or at

rest

Also called “Acute Heart Failure Syndromes”

Poor prognosis: mortality 1 year post discharge can be as high as 30%

Subgroups include entities such as HF + Acute Coronary Syndromes, shock, acutely worsening right HF, postoperative HF decompensation, and accelerated hypertension with acutely decompensated HF

Definition: Rapid or gradual development of HF signs and symptoms requiring urgent therapy

CONSENSUS (Enalapril v. placebo)SOLVD (Enalapril v. placebo)SAVE (Captopril v. placebo)POST MI TRIALS

AIRE TRACE ISIS IV GISSI 3 CHINESE CAPTOPRIL TRIAL

CLASS I ACE inhibitors are recommended in

patients with HFrEF and current or prior symptoms, unless contraindicated, to reduce morbidity and mortality (Level of Evidence A)

Use in all patients with LVEF <40% (both Asymptomatic LV Dysfunction and HFrEF of any NYHA class)

Start with low dose and uptitrate slowly (i.e., every two weeks) after evaluating K, renal function, and orthostasis

Uptitrate to the optimally tolerated dose, with the goal dose same as the dose used in trials

Val-HeFT (Valsartan v. placebo) VALIANT (Valsartan v. Valsartan +

Captopril v. Captopril in post MI patients LVEF <35-40%

HEAAL (high dose losartan v. low dose losartan)

CHARM ADDED (Candesartan v. placebo)

CHARM ALTERNATIVE (Candesartan v. placebo)

CLASS I ARBs are recommended in patients with

HFrEF with current or prior symptoms who are ACEI intolerant, unless contraindicated, to reduce morbidity and mortality (Level of Evidence A)

CLASS IIa ARBs are reasonable to reduce morbidity

and mortality a alternatives to ACEI as first-line therapy for patients with HFrEF, especially for patients already taking ARBs for other indications, unless contraindicated (Level of Evidence A)

CLASS IIb Addition of an ARB may be considered in

persistently symptomatic patients with HFrEF who are already being treated with an ACEI and a beta blocker in whom an aldosterone antagonist is not indicated or tolerated (Level of Evidence A)

CLASS III: HARM Routine combined use of an ACEI, ARB,

and aldosterone antagonist is potentially harmful for patients with HFrEF (Level of Evidence C)

It is recommended to use ARBs in ACEI-intolerant patients (due to cough and PERHAPS angioedema) with NYHA I-IV HFrEF ARBs are reasonable as alternatives to ACEI as

first-line therapy in HFrEF Only 3 ARBs have been studied in HFrEF

(Valsartan, Losartan, and Candesartan) Uptitrate to the doses used in the trials If ACEI is contraindicated due to

hyperkalemia or renal insufficiency, use nitrate-hydralazine combination. DO NOT USE ARB IN THIS SETTING.

U.S. CARVEDILOL HEART FAILURE STUDY

CAPRICORN (Carvedilol v. placebo) COPERNICUS (Carvedilol v. placebo) COMET (Carvedilol v. Metoprolol

Tartrate) CIBIS II (Bisoprolol v. placebo) MERIT-HF (Metoprolol Succinate CR/XL

v. placebo) SENIORS (Nebivolol v. placebo)

CLASS I Use of 1 of the 3 beta blockers proven

to reduce mortality (i.e., bisoprolol, carvedilol, and sustained-release metoprolol succinate) is recommended for all patients with current or prior symptoms of HFrEf, unless contraindicated, to reduce morbidity and mortality (Level of Evidence A)

Use in all patients with LVEF <40% (both HFrEF and asymptomatic LV dysfunction all NYHA classes

Use only evidence-based beta blockers. Not all beta blockers are alike

Start at low dose and uptitrate slowly (i.e., every two weeks) after evaluating for bradycardia, AV block, hypotension, congestion, and fatigue

Uptitrate to the doses used in the trials. DO NOT STOP UPTITRATING JUST BECAUSE THEY ARE ASYMPTOMATIC!

CLASS I Diuretics are recommended in

patients with HFrEf who have evidence of fluid retention, unless contraindicated, to improve symptoms (Level of Evidence C)

DOSE Low dose infusion v. low dose

intermittent bolus v. high dose infusion v. high dose intermittent bolus in patients with Acute Decompensated Heart Failure

Use for symptomatic relief of systemic or pulmonary congestion

Diurese until dry and at the correct rate, then institute maintenance dose

Best strategy for maintenance diuretic is to prescribe a weight-based diuretic dose

Must combine diuretic with a low Na diet Monitor electrolytes, renal function, and

orthostatic symptoms and signs closely

RALES Spironolactone v. placebo

EPHESUS Eplerenone v. placebo

EMPHASIS-HF Eplerenone v. placebo

CLASS I Aldosterone receptor antagonists (or

mineralocorticoid receptor antagonists) are recommended in patients with NYHA class II-IV and who have LVEF of <35%, unless contraindicated, to reduce morbidity and mortality (Level of Evidence A)▪ Patients with NYHA II should have a history of

prior cardiovascular hospitalization or elevated plasma natiuretic peptide levels to be considered for aldosterone receptro antagonists.

CLASS I ▪ Creatinine should be <2.5 mg/dL in men or

<2.0 mg/dL in women (or estimated GFR > 30 mL/min/1.73 sq. meters), and potassium should be < 5.0 mEq/L. ▪ Careful monitoring of potassium, renal

function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyprekalemia and renal insufficiency

CLASS I Aldosterone receptor antagonists are

recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of <40% who develop symptoms of HF or who have a history of DM, unless contraindicated (Level of Evidence B)

CLASS III Inappropriate use of aldosterone

receptor antgonists is potentially harmful because of life-threatening hyperkalemia or renal insufficiency when serum creatinine is > 2.5 mg/dL in men or> 2.0 mg/dL in women (or estimated glomerular filtration rate < 30 mL/min/1.73 sq. meters) (Level of Evidence B)

Use to reduce mortality and morbidity in NYHA II-IV HFrEF + LVEF <35% + already on ACEI (or ARB) and evidence beta blocker Start in NYHA II HFrEF only if BNP is elevated or previous

CV hospitalization Use post-MI beginning day 3-14 x 1 year (at least) to

reduce mortality and morbidity in patients with LVEF<40% + symptoms of HF or presence of DM

Remember the contraindications to aldosterone antagonists, and DO NOT COMBINE ACE + ARB+ ALDOSTERONE ANTAGONIST

Once initiated, check K and renal function 3 and 7 days later, q 1 month x3, then q 3 months thereafter. Restart the cycle with any change of dose of ACEI (or ARB), diuretic, or aldosterone antanonist

V-HeFT ISDN/hydralazine v. prazosin v. placebo

A-HeFT ISDN/Hydralazine v. placebo

CLASS I The combination of hydralazine and

isosorbide dinatrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III-IV HFrEF receiving optimal therapy with ACEI and beta blockers, unless contraindicated (Level of Evidence A)

CLASS IIa A combination of hydralazine and

isosorbide dinatrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated (Level of Evidence B)

Use the combination to reduce mortality and morbidity in African Americans + HFrEF +NYHA III-IV +already on optimum therapy with evidence-based beta blockers, ACEI (or ARB), and aldosterone antagonist

Use the combination to reduce mortality and morbidity in HFrEF + contraindication to ACEI or ARB (due to hypotension, renal insufficiency, or drug intolerance)

DIGITALIS INVESTIGATION GROUP (DIG) TRIAL

DIGOXIN WITHDRAWAL TRIALS RADIANCE PROVED

CLASS IIa Digoxin can be beneficial in patients

with HFrEF, unless contraindicated, to decrease hospitalizations for HF (IIa, Level of Evidence B)

Digoxin is indicated for HFrEF patients already treated with ACEI (or ARB), evidence based beta blockers, aldosterone antagonist, diuretic, and persistent NYHA II-IV symptoms to reduce rehospitalization

If the patient with HFrEF is stable on digoxin with an appropriate level, do not discontinue

Keep the digoxin level between 0.5-0.9

WATCH Warfarin v. aspirin v. clopidogrel

WARCEF Warfarin v. asppirin

CLASS I Patients with chronic HF with

permanent/ persistent/ paroxysmal AF and an additional risk factor for cardioembolic stroke (history of hypertension, DM, previous stroke or TIA, or > 75 years of age) should receive chronic anticoagulant therapy (Level of Evidence A)

CLASS I The selection of an anticoagulant agent

(warfarin, dabigatran, apixaban, or rivaroxaban) for permanent/ persistent/ paroxysmal AF should be individualized on the basis of risk factors, cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics, including time in the INR therapeutic range if the patient has been taking warfarin (Level of Evidence C)

CLASS IIa Chronic anticoagulation is reasonable

for patients with chronic HF who have permanent/ persistent/ paroxysmal AF but are without an additional risk factor for cardioembolic stroke (Level of Evidence B)

Chronic HFrEF + Atrial Fibrillation (paroxysmal, persistent, or permanent) + one additional risk factor for cardioembolic stroke should receive chronic anticoagulant therapy (hypertension, age>75,DM, prior stroke or TIA)

The selection of an anticoagulant agent (Dabigatran, Rivaroxaban, Apixiaban, or Warfarin) should be individualized

HFrEF + Atrial Fibrillation (paroxysmal, persistent, or permanent) with NO additional risk factors for cardioembolic stroke is reasonable

Anticoagulation is NOT recommended in patients with chronic HFrEF without AF, a prior thromboembolic event, or a cardioembolic source

GISSI-HF Fish oil v. placebo

CLASS IIa Omega-3 polyunsaturated fatty acid

(PUFA) supplementation is reasonable to use as adjunctive therapy in patients with NYHA class II-IV symptoms and HFrEF or HFpEF, unless contraindicated to reduce mortality and cardiovascular hospitalizations (Level of Evidence B)

Omega-3 PUFA supplementation is reasonable to use as adjunctive therapy in HFrEF or HFpEF patients with NYHA II-IV to reduce mortality and cardiovascular hospitalizations

The appropriate dose of Omega-3 PUFA is 1 gram daily containing 850 mg eicosapentaenoic acid and 882 mg docosahexaenoic acid both as ethyl esters

MADITAVIDMADIT-IIDEFINITESCD-HeFT

CLASS I ICD therapy is recommended for primary

prevention of sudden cardiac death to reduce total mortality in selected patients with nonischemic DCM or ischemic heat disease at least 40 days post-MI with LVEF< 35% and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for more than 1year (Level of Evidence A)

CLASS I ICD therapy is recommended for primary

prevention of sudden cardiac death to reduce total mortality in selected patients at least 40 days post-MI with LVEF < 30% and NYHA class I symptoms while receiving GDMT, who have reasonable expectation of menaingful survival for more than 1 year (Level of Evidence B)

CLASS IIb The usefulness of implantation of an ICD

is of uncertain benefit to prolong meaningful survival in patients with a high risk of non-sudden death as predicted by frequent hospitalizations, advanced frailty, or comorbidities such as systemic malignancy or severe renal dysfunction (Level of Evidence B)

CLASS I LVEF < 35% + GDMT +NYHA II and III LVEF < 30% + GDMT + NYHA I +

Ischemic CM

MUSTICMIRACLEMIRACLE-ICDCOMPANIONCARE-HFMADIT-CRTRAFTBLOCK HF

CLASS I CRT is indicated for patients who have

LVEF<35%, sinus rhythm, left bundle-branch block (LBBB) with a QRS duration of > 150 msec, and NYHA class II, III, or ambulatory IV symptoms on GDMT (Level of Evidence B)

CLASS IIa CRT can be useful for patients who have

LVEF <35%, sinus rhythm, a non-LBBB pattern with QRS of > 150 msec, and NYHA class III/ambulatory class IV (Level of Evidence A)

CRT can be useful for patients who have LVEF <35%, sinus rhythm, LBBB with a QRS duration of 120-149 msec, and NYHA class II, III, or ambulatory IV symptoms on GDMT (Level of Evidence B)

CLASS IIa CRT can be useful in patients with AF

and LVEF <35% on GDMT if:▪ The patient requires ventricular pacing or

otherwise meets CRT criteria

AND▪ Atrioventricular nodal ablation or

pharmacological rate control will allow near 100% ventricular pacing with CRT (Level of Evidence B)

CLASS IIa CRT can be useful for patients on GDMT

who have LVEF <35%, and are undergoing placement of a new or replacement device with anticipated requirement for significant (>40%) ventricular pacing

CLASS IIb CRT may be considered for patients who

have LVEF <35%, sinus rhythm, a non-LBBB pattern with QRS duration of 120-149 ms, and NYHA class III/ambulatory class IV on GDMT (Level of Evidence B)

CRT may be considered for patients who have LVEF <35%, sinus rhythm, a non-LBBB pattern with a QRS duration of > 150 msec, and NYHA class II symptoms on GDMT (Level of Evidence B)

CLASS IIb CRT may be considered for patients who

have LVEF of < 30%, ischemic etiology of HF, sinus rhythm, LBBB with a QRS duration of > 150 msec, and NYHA class I symptoms on GDMT

CLASS III (NO BENEFIT) CRT is not recommended for patients

with NYHA class I or II symptoms and non-LBBB pattern with QRS duration < 150 msec (Level of Evidence B)

CRT is not indicated for patients whose comorbidities and/ or frailty limit survival with good functional capacity to < 1 year (Level of Evidence C)

REQUIREMENTS: LVEF <35% Must be on GDMT Must have QRS duration > 120 msec Must be NYHA class III or ambulatory IV▪ Indicated for NYHA II only with LBBB and QRS

> 150 msec ▪ Never indicated for NYHA 1

LVEF <35% + GDMT +NSR +LBBB WITH QRS >120 + NYHA II, III, AMBULATORY IV

LVEF <35% + GDMT + NSR +NON LBBB+ QRS >150 + NYHA III, AMBULATORY IV

LVEF <35% + GDMT + AF + OTHERWISE MEETS REQUIREMENTS FOR CRT OR REQUIRES PACEMAKER: After AVN ablation or pharmacologic rate

control requireing 100% pacing Already has RV pacemaker pacing > 40% of

rhythm

J Am Coll Cardiol 2013;62:1495-1539 (Executive Summary)

J Am Coll Cardiol 2013; 62: e147-239 (Full Text)

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SOLVD N Engl J Med. 1991; 5:293-302.

SAVE N Engl J. Med. 1992; 10: 669-77.

AIRE Lancet. 1993; 342: 821-828.

TRACE N Engl J Med. 1995; 25: 1670-6.

ISIS 4 Lancet. 1995; 345 : 669-85.

GISSI 3 Lancet. 1994; 343:1115-22.

Val-HeFT N Engl J Med. 2001;345:1667-75.

CARM-Added Lancet. 2003; 362:767-71.

CHARM-Alternative Lancet. 2003; 362: 772-6.

CHARM-Preserved Lancet. 2003; 362: 777-81.

VALIANT N Engl J Med. 2003;349: 1893-906.

I-PRESERVE N Engl J Med. 2008; 23: 2456-67.

HEAAL Lancet. 2009 374: 1840-8.

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CIBIS-II Lancet. 1999; 353: 9-13.

MERIT-HF Lancet. 1999; 353: 2001-7.

CAPRICORN Lancet. 2001; 357: 1385-90.

COPERNICUS N Engl J Med. 2001; 344: 1651-8.

COMET Lancet. 2003; 362: 7-13.

SENIORS Eur. Heart J. 2005; 3:215-25.

RALES N Engl. J Med. 1999; 341: 709-17.

EPHESUS N Engl. J Med. 2003; 348: 1309-21.

EMPHASIS-HF N Engl J Med. 2011; 364:11-21.

V-HeFT N Engl J Med. 1986; 314: 1547-52.

A-HeFT N Engl J Med. 2004; 351: 2049-57.

DIG N Engl J Med. 1997; 336: 525-33.

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WARCEF N Engl. J Med. 2012;

GISSI-HF Lancet. 2008; 372: 1223-30.

FAIR-HF N Engl J Med. 2009; 361: 2436-48.

RED-HF N Engl J Med. 2013: 368: 1210-9.

MADIT N Engl J Med. 1996; 335:1933-40.

AVID N Engl J Med. 1997; 337: 1576-1583.

MADIT-II N Engl J Med. 2002; 346: 877-83.

DEFINITE N Engl. J Med. 2004; 350: 2151-8.

SCD-HeFT N Engl J Med. 2005; 352: 225-37.

MUSTIC N Engl J Med. 2001; 344: 873-80.

MIRACLE N Engl J Med. 2002; 346: 1845-53.

MIRACLE-ICD JAMA. 2003; 289: 2685-94

COMPANION N Engl J Med. 2004; 350: 2140-50.

CARE-HF N Engl J Med. 2005; 352: 1539-49.

RethinQ N Engl J Med. 2007; 357: 2461-71

MADIT-CRT N Engl J Med. 2009; 361: 1329-38.

RAFT N Engl J Med. 2010: 363: 2385-95.

BLOCK HFN Engl J Med. 2013; 368: 1585-1593.

PRAISE N Engl J Med. 1996; 335: 1107-14

SHIFT Lancet. 2010: 376: 875-85.

EVEREST JAMA. 2007; 297: 1319-31.

RELAX JAMA. 2013: 309: 1268-77.

GESICA Lancet. 1994; 344: 493-98.

CHF-STAT N Engl J Med. 1995; 333: 77-82

DIAMOND-CHF N Engl J Med. 1999; 341: 857-65.

SCD-HeFT N Engl J Med 2005; 352: 225-37.

ANDROMEDA N Engl J Med. 2008; 358: 2678-87.

PABA-CHF N Engl J Med. 2008; 359: 1778-85.

AF-CHF N Engl J Med. 2008; 358: 2667-2677

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REMATCH N Engl J Med. 2001; 345; 1435-43

Heartmate II N Engl J Med. 2009; 361: 2241-51.

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STITCH-2 N Engl J Med. 2009; 360: 1705-17.

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Tele-HF N Engl J Med. 2010; 363: 2301-9.

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HART JAMA. 2010; 304: 1331-38.

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