LITERATURE REVIEW: HEART FAILURE Chief Residents

Heart Failure

EF ≤ 40% “HFrEF” Problem with contractility

EF 40-50% “HFmrEF”

EF > 50% “HFpEF” Problem with filling/relaxation

RISK FACTORS •  Post MI •  HTN •  DM •  Obesity •  OSA

SYMPTOMS AND SIGNS

Symptoms Mechanism

SOB Pulmonary congestion 2/2 increased LA pressure

Orthopnea, PND Increased venous return and lung congestion in supine position

Palpitations Tachyarrhythmias

Anorexia, Cachexia, Early Satiety

Fluid retention, ingestional congestion, chronic inflammatory pathway activation

Signs Mechanism

Elevated JVP Increased RA pressure

Holosystolic murmur MR or TR

S3 gallop Increased LA pressure

Pulmonary crackles, pleural effusion

Increased atrial pressure, congestion

Hepatomegaly, hepatojugular reflex, ascites

Increased RA pressure

Peripheral edema fluid retention

DIAGNOSTIC TOOLS

•  TTE (EF, wall motion, valvular disease) •  EKG •  CXR •  Troponin •  BNP

•  Falsely low in obese •  Falsely high in elderly

DIURETICS

Diuretic PO IV

Furosemide 40mg 20mg

Bumetanide 1mg 1mg

Torasemide 20mg 20mg

•  Bumex and Torsemide are cleared by the liver rather than the kidney

•  Bumex and Torsemide have 100% bioavailability (vs. variable with Furosemide)

•  TORIC study: compared Torasemide (10mg) vs. Furosemide(40mg)/Other diuretics (not bumetanide) •  Torasemide well-tolerated, improved functional

status, decreased overall mortality •  Not a therapeutic dose of torasemide

•  Gut wall edema à decreased absorption of PO •  IV for all hospitalized patients with ADHF (Class I)

•  DOSE trial (2011): continuous vs spot dose IV infusion (EF < 35%) •  No change in patient-reported symptoms, change in creatinine,

weight change, NT-proBNP levels, LOS, all-cause mortality, or re-hospitalization

•  “high dose” (2.5x home dose) vs “low dose” (home dose converted to IV equivalent) showed higher rates of Cr elevation but improved fluid reduction, decrease in NT-proBNP, and weight loss at 72hrs

•  Dopamine? Low dose à renal protection? •  DAD-HF trial (2010): low-dose Lasix + low dose

dopamine vs high-dose Lasix in HFrEF •  No change in urine output, dyspnea scores, LOS, mortality, re-

hospitalization rates; LDLD had better renal profile (lower change in Cr, lower drops in K)

•  Class IIB: consider addition of dopa to improve diuresis

BETA BLOCKERS •  Bisprolol

•  CIBIS-II (1999): addition of bisoprolol to standard therapy decreases all-cause mortality in patients with HFrEF (EF ≤ 35%)

•  Metoprolol Succinate •  MERIT-HF (1999): in patients with EF ≤ 40%, MTP XL reduces all-cause

mortality compared to placebo •  Carvedilol

•  COPERNICUS (2002): addition of carvedilol decreases mortality and hospitalizations compared to placebo in patients with HFrEF (EF ≤ 25%)

•  MTP vs Carvedilol? •  COMET (2003): coreg decreases all-cause mortality compared

with MTP •  Used MTP tartrate; used inequivical doses of coreg and MTP

•  Retrospective study 2015 compared coreg and MTP succinate; after multivariate adjustment no change in survival

•  CO = HR x SV; in ADHF, SV so don’t decrease HR (further worsen CO)

ACE-I/ARB •  All patients with HFrEF should be on ACE-I or ARB (if ACE-I

intolerant) to reduce mortality •  AKI is relative contraindication, CKD ok if Cr < 2.5 in

males and < 2.0 in females with K < 5.0

•  CONSENSUS (1987): NYHA IV HF showed reduction in mortality at 12mo with initiation of enalapril compared to placebo

•  SOLVD (1991): NYHA 1-IV (primarily II, III) with EF ≤ 35%, use of enalapril showed reduction in CV-related hospitalization and mortality

•  CHARM (2003): NYHA II-IV with EF ≤ 40%, patients who were intolerant to ACE-I were placed on candesartan with reduction in hospitalization for HF and CV-mortality compared to placebo

Aldosterone Antagonists ACC guidelines:

•  Aldosterone antagonists recommended for NYHA class II-IV with LVEF ≤ 35% •  RALES (1999): NYHA III, IV and EF ≤ 35% the addition of spironolactone vs placebo

decreased all-cause mortality without significant increase in hyperkalemia or renal failure

•  EMPHASIS-HF (2011): NYHA II-IV, the addition of eplerenone to standard therapy reduces CV death or HF-related hospitalization

•  Aldosterone antagonists recommended after MI if EF ≤ 40% if patient has sx of HF or hx of DM •  EPHESUS (2003): in patients with reduced EF (≤ 40%) following acute MI, addition of

eplerenone decreased sudden cardiac death and hospitalization when combined with standard therapy

NEPRILYSIN INHIBITORS

“ARNI”: Angiotensin Receptor –Neprilysn Inhibitor

PARADIGM-HF (2014): •  f/u on OVERTURE (2002), which showed

omapatrilat reduced mortality and hospitalization compared to ACE-I

•  Entresto vs enalapril •  NYHA II-IV, EF ≤ 40 à 35% (2010) •  Stable on ACE-I/ARB •  Reduction in all-cause mortality, CV-mortality, or

HF-related hospitalization

•  2017 ACC guidelines: •  In patients with NYHA II/III HFrEF tolerating

ACE-I/ARB therapy should be switched to ARNI for morbidity and mortality benefit

Ivabradine

Reduces HR independent of BB

•  SHIFT (2010): •  EF ≤ 35%, NYHA II-IV, resting HR > 70

despite max medical therapy including beta blockers

•  5% absolute reduction in HF-hospitalization and 2% absolute reduction in HF-related mortality

•  ACC (2017): Ivabradine can be beneficial to reduce HF hospitalization for patients with NYHA II/III HFrEF who are on guideline-based therapy with max-tolerated beta blocker and in NSR with resting HR > 70 (class IIb)