Definition

Heart failure is a clinical diagnosis. It is a syndrome resulting from structural or functional impairment of ventricular filling or ejection of blood such that the body’s metabolic demands cannot be met. It often involves elevated filling pressures and a propensity to retain volume. An elevated BNP (or NT-proBNP) and TTE showing cardiac dysfunction can be helpful in supporting the diagnosis, but ultimately it is a clinical diagnosis.

Classification

• Most important classification involves dichotomy between preserved (HFpEF; EF≥50) and reduced ejection fraction (HFrEF; EF≤40) phenotypes, as that directs ultimate long-term therapy.
• NYHA and AHA/ACC are used to classify severity by functional status and stage in progression, respectively.

• Transthoracic echocardiogram (TTE) important to establish phenotype (HFrEF vs HFpEF).
  • Repeat measurement useful in patients with significant change in clinical status.
• Ischemia is the most common cause of heart failure in US – all patients with new diagnosis of HF should have evaluation for underlying ischemia (noninvasive imaging unless patient presents with angina, VT, or cardiac arrest).
• Non-ischemic etiologies:
  • Mechanisms affecting preload/afterload of left heart: chronic HTN, aortic stenosis, aortic regurgitation, mitral regurgitation.
  • Mechanisms affecting rhythm: tachycardia mediated, chronic RV pacing.
  • TIMIGS mnemonic:
    • Toxin: EtOH/meth/cocaine, chemotherapy, radiation.
    • Inflammation:
      • Infection: viral myocarditis, Chagas, HIV.
      • Inflammatory conditions (e.g. SLE).
    • Metabolic: thiamine (beri beri) causing high output failure.
    • Infiltrative: amyloid, hemochromatosis, sarcoid.
    • Genetic.
    • Stress: Takutsubo, sepsis, peripartum.
• HFpEF often associated with systemic hypertension, aging, obesity, DM/metabolic syndrome.
• Etiologies of exacerbations:
  • Cannot miss: new ischemia or new valvular pathology.
  • Others to consider: poor dietary and/or medication adherence, inadequate drug therapy, HTN, arrhythmia (e.g., atrial fibrillation/flutter), medications that increase sodium retention (e.g. NSAIDs, corticosteroids), anemia, AKI, myocarditis/pericarditis, substance use, PE, infection, hyper/hypothyroidism, physical or emotional stress.

• Review old TTE, stress tests, ECGs, and cath reports.
• History:
  • Symptoms: dyspnea, orthopnea, PND, edema, abdominal discomfort/fullness, nausea, anorexia, weight change).
  • Medication history including recent changes and missed doses.
  • Substance history (stimulants and alcohol).
  • Dietary indiscretion.
• Physical examination:
• Evaluate perfusion (cold vs warm): altered mental status, Cheyne-Stokes respirations, pallor, cool extremities, narrow pulse pressure.
• Evaluate for congestion (wet vs dry):
  • Left-sided congestion: crackles (pulmonary edema), left ventricular S3, elevated JVP.
  • Right-sided congestion: elevated JVP, hepato-jugular reflex, dilated and non-collapsible IVC (>2.1 cm, <50% collapsible), pulsatile liver, right ventricular S3, lower extremity edema (poor surrogate for intravascular volume).

• Workup for suspected new or worsening HF as cause of dyspnea:
  • Labs: CBC, chem-10, troponin, BNP, lactate.
  • CXR, EKG, POCUS, TTE.
  • If unknown underlying etiology consider lipid panel, HgbA1c, HIV, UTox, TSH.
  • Evaluation for underlying etiology depends on pre-test probability of ischemia and may include noninvasive stress test, cardiac CT angiography, coronary angiography, or CMR.

• Causes of falsely high/low BNP:
  • BNP is elevated in advancing age and non-cardiac conditions: anemia, renal failure, PH, critical illness, sepsis.
  • BNP can be lowered in obesity, constrictive pericarditis, diuretics, ACE inhibitors, beta-blockers, and MRA.
  • ARNI can cause elevation in BNP (and not NT-proBNP) early after initiation but after 8 weeks has equal prognostic value to NT-proBNP.

Therapy should be tailored to the hemodynamic profile as described in the chart below:

	Warm	Cold (hypoperfusion)
Wet	Acute care vs TCU IV diuresis Afterload reduction Ok to continue BB if previously on	ICU level IV diuresis (ultrafiltration if refractory) Afterload reduction Inotrope or Inodilator Advanced therapies for cardiogenic shock
Dry	Outpatient GDMT	Afterload reduction Inotrope or Inodilator Advanced therapies for cardiogenic shock

Supportive care:

• Telemetry monitoring (with CPO) with supportive O2 (+/- NIPPV) for hypoxemia.
• Monitor K, Mg, BUN/Cr and replete K>4, Mg>2 daily. Sometimes checked BID during IV diuresis.
• Restrict sodium (<2g) and also fluids (<1500cc); daily standing weights, strict I&Os.
• TED hose and lower extremity elevation for swelling.
• DVT ppx unless contraindicated.

Diuretics:

• General principles:
  • Diuretics are threshold drugs – increasing dose above ceiling extends time above natriuretic threshold but does not increase rate of diuresis.
  • Patients experience decreased natriuretic response to subsequent doses of the same diuretic due to extracellular fluid depletion, SNS/RAAS activation, and nephron remodeling.
  • As patients approach euvolemia, rate of diuresis may need to slow to accommodate re-equilibration of extravascular and intravascular fluid compartments.
• Start with 2.5 x equivalent home dose (DOSE trial) of loop diuretic. If diuretic naïve, start with 20-40mg IV furosemide.
  • Do not hold diuretics for low BP or initial increase sCr if patient is still intravascularly congested.
  • Double previous dose if poor response.
  • Ensure adequate afterload reduction with ACE/ARB, hydralazine.
• Loop diuretic equivalencies:
  • 20mg IV furosemide = 40mg PO furosemide = 1mg IV/PO bumetanide = 20mg IV/PO torsemide.
  • Duration of action (dosing interval):
    • Furosemide: 6-8 hours.
    • Bumetanide: 4-6 hours.
    • Torsemide: 12 hours.
• Diuretic resistance:
  • Sequential nephron blockade with thiazide (metolazone or chlorothiazide).
    • Metolazone should precede morning loop diuretic by 1 hour.
  • Loop diuretic gtt: give loading dose (bolus) prior to initial dose and when changing rate.
    • Furosemide gtt: initial 20-80mg IV bolus (higher doses for patients with worse renal function; lower doses for diuretic naïve patients). Then start gtt at 5mg/hr (range 5-20mg/hr). FENa can be monitored to determine effectiveness of natriuresis (maximum FENa = 20%).
    • Bumetanide gtt: initial 1-2mg bolus. Then start gtt at 0.5mg/hr (range 0.2-2mg/hr).
  • Consider low dose dobutamine gtt (see below).
  • Ultrafiltration for patients with obvious volume overload and refractory congestion.
• I/O goals depend on both clinical volume assessment and cardiac substrate:
  • Aggressive (3-4L negative) in severe volume overload and HFrEF.
  • Conservative (1.5-2L negative) in mild volume overload, restrictive cardiomyopathy or HFpEF.
  • When euvolemic, switch to PO diuretic with goal even to -500ml.

Vasodilators:

• Not for routine use. May be required for urgent correction of afterload or filling pressures (preload), in non-hypotensive patients (SBP>90).
• Nitroprusside:
  • Balanced venous and arterial vasodilation for rapid correction of hypertensive emergency.
  • Requires continuous (invasive) blood pressure monitoring with arterial line.
  • Nitroprusside gtt: initial 5-10mcg/min and titrate every 5 min.
  • Side effects: cyanide (accumulates in liver dysfunction) and thiocyanate (metabolite accumulates in renal dysfunction) toxicity that can cause nausea, abdominal discomfort, dissociative feelings, dysphoria.
  • Use caution if suspect coronary ischemia because intramyocardial vasodilation can result in coronary steal.
• Nitroglycerin:
  • Predominantly venous dilation (arterial dilation at higher doses) for rapid relief of pulmonary congestion and myocardial oxygen demand.
  • Avoid in patients taking PDE5 inhibitors (e.g. sildenafil).
  • Tachyphylaxis occurs in 24-48 hours; common side effects are headache and hypotension.

Inotropes and inodilators:

• See section Cardiogenic Shock for details.
• Requires continuous hemodynamic monitoring including central access.
• Dobutamine:
  • Most common inotrope used in AHF. Also causes vasodilation that can reduce afterload, improve renal perfusion (and therefore augment diuresis) and preload.
  • Side effects: increased chronotropy and tachyarrhythmia (AF/RVR), worsen myocardial O2 demand.

Advancing guideline-directed medical therapy (GDMT) in the hospital:

• Prioritize diuresis and afterload reduction initially.

• Outpatient MRA and ACE are often withheld in the setting of reduced renal function but can be restarted once stabilized.
• Continue outpatient beta blockade if not in shock or hypotensive.
  • Defer initiating or uptitrating beta blockade until improved decongestion.
  • For patients with afib with RVR, ok to initiate low dose beta blockade (or amiodarone or digoxin) but avoid non-dihydropyridine CCB (e.g. diltiazem).

All patients admitted for AHF should be started/titrated on goal-directed medical therapy (GDMT) to reduce rates of readmissions and improve long-term outcomes. GDMT should be initiated at low doses and can be slowly up-titrated as tolerated, with the intention of starting as many medications as able. All of these below provide mortality and CV benefit unless otherwise noted.

• ACE inhibitors/ARB/ARNI: provide afterload reduction and reduce counterproductive neuro-hormonal adaptations. All patients with HFrEF should be on one of these (ARNI such as sacubitril/valsartan [Entresto] may be favored based on PIONEER-HF trial; sometimes difficult to authorize as inpatient).
  • Of note, if likely to start Entresto as outpatient should consider starting an ARB initially  since ACE inhibitors require washout period of 36 hours prior to initiating ARNI to reduce risk of angioedema.
  • For ACEi, can start with captopril 3.125 mg scheduled q8h and titrate as tolerated with conversions below. Monitor for hypotension.

Captopril	Enalapril	Benazapril, Fosinopril, Lisinopril
6.25 mg q8h	n/a	5 mg daily
12.5 mg q8h	5 mg q12h	10 mg daily
25 mg q8h	10 mg q12 h	20 mg daily
50 mg q8h	20 mg q12h	mg daily

• Target dosing: lisinopril 40mg PO daily. Entresto (sacubitril/valsartan): 97/103 BID.

• Beta-blockers: hemodynamic benefits, reduce maladaptive LV remodeling, decrease frequency of PVCs.
  • Metoprolol ER, carvedilol, and bisoprolol have symptom and mortality benefit and slow disease progression for NHYA class II-IV chronic HF. 
  • If patient on home BB, can continue as long as not in cardiogenic shock or requiring inotropes.
  • Starting doses: metoprolol tartrate 12.5mg given BID/q6h, carvedilol 3.125mg PO BID, titrate up as BP and HR allow.
  • Target dosing: metoprolol ER 200mg daily or carvedilol 25mg BID (50mg BID if >85kg). 
• Mineralocorticoid receptor antagonists (MRA): survival benefit for EF <35% and hospitalization benefit for HFpEF. Guideline recommended for EF <35% or <40% following MI.
  • Contraindications: GFR <30 (dose reduce 30-50), difficulties with hyperkalemia.
  • Initial dosing: spironolactone 25mg daily (12.5mg ok if GFR 30-50).
  • Can consider changing to eplerenone (much more expensive) if undesired endocrine side effects (e.g. gynecomastia) with spironolactone. 
  • Monitor K+ closely.
• SGLT2 inhibitors: during initial trials to evaluate cardiac safety of SGLT2 inhibitors for patients with DM, they were found to have robust mortality/CV benefit even when patients were already on GDMT. Subsequent trials for patients without DM have confirmed benefit even outside of diabetes so movement now towards starting this medication if possible in patients admitted for AHF.
  • Contraindication: GFR <45.
  • Dosing dependent on which SGLT2 inhibitor is being used. Dapagliflozin (the first approved for HFrEF in patients without DM): initial 5mg daily, goal 10mg.
  • Monitoring: initiation of SGLT2 inhibitors may have increased diuretic effect and diuretic regimen may need adjustment. Other side effects include UTI, yeast infections, and (rare) euglycemic DKA in patients with diabetes.
• Hydralazine + nitrates:
  • Controversy about indication – trials were prior to modern GDMT and showed mortality benefit in self-identified African-American patients with non-significant trend toward improvement in non-African-American.
  • Current guidelines recommend combination for self-described African-Americans with NYHA III-IV (Class 1) or for patients in whom an ACE/ARB cannot be given because of adverse effect (Class 2b).
  • Initial dosing: hydralazine 25mg TID + isosorbide dinitrate 20mg TID or combination isosorbide dinitrate-hydralazine 37.5mg-20mg TID. Titrate up every 2-4 weeks as permitted by BP.
  • Target dosing: hydralazine 75mg TID + isosorbide dinitrate 40mg TID.
  • Can consider isosorbide mononitrate (30-120mg daily) as alternative to TID-dosed isosorbide dinitrate.
• Diuretics: no mortality benefit though provide symptom relief and required for most patients to avoid fluid accumulation.

ICD and CRT – refer if patient’s EF <35% and after at least 3 months of GDMT (NOT for any new diagnoses of heart failure).

• Implantable cardiac defibrillator (ICD): primary prevention of sudden cardiac death in populations at increased risk for life-threatening ventricular arrhythmias. Mortality benefit for NYHA class II-III HF + LVEF ≤ 35% despite optimal medical management for at least 3 months.
  • Note: there is controversy and practice variation in utilization of ‘life vest’ which provide external ICD functionality for patients during the 3 month trial of optimal medical management.
• Cardiac resynchronization therapy (CRT): HF frequently leads to intraventricular conduction delay and ventricular dyssynchrony. Resynchronization (biventricular pacing) improves pump function with mortality benefit, symptom improvement, and decreased hospitalizations for NYHA class II-III HF + LVEF ≤ 35% + LBBB + QRS ≥ 150 ms despite optimal medical management.

Comorbidities

• Atrial fibrillation:
  • Patients with atrial fibrillation and HFrEF should be evaluated for catheter ablation since this may improve outcomes over optimal medical treatment alone (CASTLE-AF).
• Sleep disordered breathing:
  • OSA is highly prevalent in patients with HF and warrants evaluation with sleep study.
• Hypertension:
  • Blood pressure goal for patients with HF or at risk for HF (ACC/AHA A) is 130/80mmHg. Uptitrate ACE/ARB/ARNI in patients with HFrEF (may consider same regimen for HFpEF).
• Anemia:
  • For patients with NYHA class II or III HF with iron deficiency (ferritin <100ng/mL or 100-300ng/mL with Tsat <20%), IV iron repletion may improve functional status and quality of life (FAIR-HF).

Palliative measures
Below are measures that can be considered for patients whose heart failure has reached end stages and cannot remain euvolemic without the addition of chronic inotropic support. Should be used in conjunction with a cardiologist with heart failure expertise. Both of these can be given in addition to beta blockers (as opposed to dobutamine):

• Milrinone: phosphodiesterase-3  inhibitor, inodilator with a longer half-life than dobutamine. Similar toxicity profile to dobutamine, and ultimately also provides no mortality benefit, but is purely to control symptoms/maintain euvolemia outside of a hospitalized setting.
• Digoxin: Na-K-ATPase inhibition improves contractility, anti-andrenergic effect also beneficial. The only safe PO inotrope. Symptomatic improvement and decrease in hospitalizations, but no mortality benefit in HF.

• Overall, HFpEF etiologies and evaluation is very similar to that of HFrEF, although ischemia is a less frequent cause compared to HFrEF.

• HF2PEF score relies on TTE and other clinical characteristics to discriminate HFpEF from non-cardiac causes of unexplained exertional dyspnea.

• Treatment:
  • Priority to treat any underlying cause of HFpEF (e.g. HTN).
  • Mainstay of therapy is diuresis for symptomatic benefit (no mortality benefit) in addition to lifestyle changes.
  • Evidence does not support any mortality benefit from medical therapy at this time (including ACE/ARB/ARNI, BB, Hydral/ISDN, SGLT2 inhibitors). MRA have been associated with decreased hospitalizations so these can be offered in accordance with guidelines.

• Steps that have been shown to reduce readmission rates:
  • Giving 24 hours of oral diuretics prior to discharge to best approximate diuretic needs.
  • Early follow-up within 7-10 days after discharge for monitoring of kidney function and electrolytes and to make diuresis adjustments as appropriate.
• Other considerations:
  • Dietary counseling about fluid and salt restriction.
  • Ensure patient has a scale and instructions regarding daily weights. Consider discharge instructions with ‘PRN’ diuretic dosing for increase in weight in addition notifying primary care provider.
  • Discuss any anticipated barriers to medication adherence with patient.

 

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