Chronic heart failure

Background

Definition

• A syndrome of volume overload and poor tissue perfusion that is caused by cardiac dysfunction and is characterized by dyspnea, fatigue, and edema

Classification by LVEF

LVEF	Classification
≤40%	Heart failure with reduced ejection fraction (HFrEF)
≤40% that improves >40% on repeat	Heart failure with improved ejection fraction (HFimpEF)
41-49%	Heart failure with mildly reduced ejection fraction (HFmrEF)
≥50%	Heart failure with preserved ejection fraction (HFpEF)

Stages

• Stage A: no structural heart disease or symptoms but high risk for developing HF (e.g., patients with diabetes mellitus or hypertension)
• Stage B: structural heart disease without symptoms of HF (e.g., patients with a previous MI and asymptomatic LV dysfunction)
• Stage C: structural heart disease with symptoms of HF (e.g., patients with a previous MI with dyspnea and fatigue)
• Stage D: refractory HF requiring special interventions (e.g., patients with refractory HF who are awaiting cardiac transplantation).

Etiologies

By Subtype

• Reduced ejection fraction (LVEF ≤40%)
  • Coronary artery disease (most common)
  • Hypertension (most common)
  • Myocarditis, including viral infection
  • Chronic alcohol use
  • Valvular heart disease
  • Chemotherapy, such as doxorubicin or trastuzumab
  • Peripartum cardiomyopathy
  • Idiopathic dilated cardiomyopathy
  • Genetic causes of cardiomyopathy
• Preserved ejection fraction (LVEF ≥50%)
  • Hypertension (most common)
  • Myocardial infarction
• Mildly reduced ejection fraction (LVEF 41-49%)

By Cardiomyopathy

• Dilated cardiomyopathy: toxins (alcohol, cocaine, chemotherapy), myocarditis, Chagas disease, peripartum cardiopmyopathy, familial cardiomyopathies
• Hypertrophic cardiomyopathy: hypertension
• Restrictive cardiomyopathy
• Arrhythmogenic right ventricular cardiomyopathy
• Unclassified cardiomyopathy: Takotsubo cardiomyopathy, non-compaction cardiomyopathy

By Risk Factor

• Common
  • Tachyarrhythmia
  • Valvular heart disease
  • If CAD risk factors:
    • Coronary artery disease
    • Hypertensive cardiomyopathy
• Other risks
  • Toxic agents: alcohol, amphetamines, cocaine, steroids, chemotherapy, heavy metals, radiation
  • Pregnancy: PPCM, pre-eclampsia, gestational diabetes
  • Inflammatory or infectious: myocarditis, sarcoidosis, infectious hypereosinophilia, giant cell lymphocytic, auto-immune diseases
  • Metabolic: diabetes, thyroid disease, adrenal insufficiency, pheochromocytoma, Cushing disease
  • Nutritional: thiamine deficiency, selenium deficiency, malnutrition, obesity
  • Infiltrative: amyloidosis, glycogen storage disease, Fabry disease
  • Hereditary: hypertrophic obstructive cardiomyopathy, ARVC, LV noncompaction, hereditary hemochromatosis
  • Acute respiratory distress syndrome (ARDS)

Epidemiology

• 6-10% of people over age 65

Risk Factors

• Previous episode of acute heart failure
• Prior atrial fibrillation or coronary artery bypass surgery
• Myocardial infarction
• Coronary artery disease
• Diabetes mellitus
• Hypertension

Clinical Manifestations

History

• History of heart failure, MI, or CAD
• Dyspnea on exertion
• Paroxysmal nocturnal dyspnea
• Orthopnea
• Fatigue
• Determine NYHA classification of functional status

Signs & Symptoms

• Cardiac exam: S3 present, abdominojugular reflux, elevated JVP
• Respiratory exam: crackles/rales
• Lower extremity edema

	Dry	Wet
Warm	Less congested Better-perfused	More congested Better-perfused
Cold	Less congested Poorly perfused	Less congested Poorly perfused

Prognosis

• Following an admission, 25% risk of 30-day readmission and 37% 1-year mortality
• 3-year all-cause mortality is 24% in HFpEF and 32% in HFrEF
• Sudden cardiac death is the cause of 50% of deaths
• Many risk calculators exist, including the MAGICC risk score

Investigations

• Lab
  • Troponins
  • B-type natriuretic peptide
    • NT-proBNP > 450 pg/mL if age < 50 years and > 900 pg/mL if age > 50 years; <100 pg/mL helps rule it out
    • Can be used in diagnosis of heart failure as a cause of dyspnea
    • Can also be used for risk stratification in patients with chronic HF and prognosis in patients admitted for HF
    • Predischarge BNP can also help with ongoing management
  • Routine initial investigations: CBC, urinalysis, electrolytes, creatinine, glucose, lipid panel, liver panel, iron studies, TSH
• Imaging
  • Chest X-ray showing pulmonary venous or interstitial edema, cardiomegaly, or pleural effusions
• Other
  • EKG showing new atrial fibrillation, ischemic changes, or any other abnormality
  • Echocardiography
    • Systolic heart failure
      • Reduced LV ejection fraction (LVEF)
    • Diastolic heart failure
      • E/A ratio less than 1
      • MV deceleration time > 220ms

Management

• See also Acute heart failure management

Non-Pharmacologic Management

• Consider referral to multidisciplinary outpatient clinic
• Diet
  • No-added-salt diet (2-3 g/day); 1-2g/day if severe fluid retention
  • Fluid limited to 1.5 L/day to 2 L/day from all sources, if diuretics fail
• Exercise: regular exercise 3-5 times a week for 30-45 min per session (after stress test)
• Lifestyle
  • Smoking cessation
  • Decrease or eliminate alcohol intake
• Monitor body weight regularly for sudden increases (e.g. 2 kg increase in 3 days)
• Pneumococcal and annual influenza vaccines
• Avoid, when possible: NSAIDs (including COX-2 inhibitors), glucocorticoids, class I antiarrhythmics, sotalol and ibutilide,TCAs, dronedarone, verapamil and diltiazem (except in HFpEF), α-blockers, moxonidine, metformin, thiazolidinediones, anthracyclines

Manage Comorbidities

• Replace iron-deficiency with IV iron (improves quality of life)
• Avoid treating diabetes with glitazones, prefer SGLT-2 inhibitors
• Treat hypertension, especially in HFpEF

Pharmacologic Treatments

• Treat cardiovascular risk factors (hypertension, dyslipidemia, atherosclerotic disease)
  • Previous MI: ASA 81 mg PO daily if indicated for secondary prevention
  • Atrial fibrillation: warfarin or other anticoagulation

HFrEF

• For symptomatic HFrEF ≤40%, the overall approach is quadruple therapy: ARNI or ACEi/ARB, β-blockers, aldosterone agonists, and SGLT2 inhibitors
  • Start with β-blocker plus SGLT2i, then ARNI, then MRA, so that they are on all four after a few weeks
    • SGLT2i has very quick benefit, regardless of diabetes, and should be started early
    • ARNIs have diuretic effect, so may need to decrease furosemide
  • Titrate up every 4 to 8 weeks
  • Monitor renal function and electrolytes 1 and 4 weeks after any increase, then monthly for 2 months, every 3 months for 9 months, and every 4 months indefinitely
• Reassess NYHA class after maximizing treatment
  • NYHA I: continue
  • NYHA II-IV and sinus rhythm with resting HR ≥70: consider adding ivabradine
  • NYHA III/IV: consider referral for advanced HF therapies including mechanical supprot
• Reassess LVEF after maximizing treatment
  • If NYHA I-III and LVEF ≤35%: consider ICD/CRT
  • NYHA IV: consider hydralazine/nitrates, referral for mechanical support or transplant, refer to palliative care
• If congestive symptoms:
  • First-line: loop diuretic at lowest minimal dose required to control symptoms
  • Second-line: consider adding thiazide or low-dose metolazone
  • Last-line: consider adding digoxin if severe symptoms or poorly-controlled atrial fibrillation

SGLT2 Inhibitors

• Contraindicated in GFR <25ish (depending on agent)
• Increased risk of genital mycotic infections

Doses

Medication	Starting Dose	Titration	Usual Dose	Notes
Diuretics: Loop
furosemide	20-40 mg/d		40-240 mg/d
torasemide	5-10 mg/d		10-20 mg/d
Diuretics: Thiazide-Like
chlorthalidone	12.5-25 mg/d		25-100 mg/d
hydrochlorothiazide	25 mg/d		12.5-100 mg/d
indapamide	2.5 mg/d		2.5-5 mg/d
Diuretics: Potassium-Sparing
amiloride	2.5 mg/d		5-10 mg/d
eplerenone	25 mg/d		50 mg/d
spirolonactone	12.5-25 mg/d		50 mg/d
β-Blockers
bisoprolol	1.25 mg daily	2.5, 3.75, 5, 7, 10
carvedilol	3.125 mg bid	6.25, 12.5, 25, 50
metoprolol succinate CR	12.5-25 mg daily	25, 50, 100, 200
Angiotensin Antagonists: ACE Inhibitors
enalapril	2.5 mg bid		10-20 mg bid
captopril	6.25 mg tid		50 mg tid
lisinopril	2.5-5 mg daily		20-35 mg daily
ramipril	2.5 mg daily		5 mg daily
trandolapril	0.5 mg daily		4 mg daily
Angiotensin Antagonists: ARBs
candesartan	4-8 mg daily		32 mg daily
valsartan	40 mg bid		160 mg bid
losartan	50 mg daily		150 mg daily
Angiotensin Antagonists: ARB/ARNI
valsartan/sacubitril	24/26 mg bid to 49/51 mg bid		97/103 mg bid	If on ACEi, need 36 hour washout period before starting
SGLT2 Inhibitors
dapagliflozin	10 mg daily		10 mg daily
empagliflozin	10 mg daily		10 mg daily
Others
ISDN and hydralazine	20-30 mg and 25-50 mg tid to qid		120 mg TDD and 300 mg TDD
ivabradine	5 mg bid		7.5 mg bid
vericiguat	2.5 mg daily		10 mg daily
digoxin	0.125-0.25 mg daily		serum concentration 0.5-0.9 ng/mL

Procedures

• Cardiac resynchronization therapy is indicated when LVEF<30%, LBBB, and QRS > 150ms
• Devices
  • ICD if EF <35%
  • CRT +/- ICD if reduced EF and LBBB
• Implantable hemodynamic monitor (CardioMEMS)
  • Pulmonary artery pressure sensor
  • Better than daily weights for predicting heart failure exacerbations
  • Reduces hospitalizations by 30%
  • Studied in HFpEF and HFrEF
  • Expensive! $20k
• Surgery: see advanced therapies, below

Advanced Therapies

• Consider advanced therapies such as left ventricular assist device or cardiac transplantation when heart failure is severe and refractory
• Possible indications include:
  • LVEF <25%
  • End-organ dysfunction
  • Recurrent hospitalizations 2x/12months unexplained
  • Unable to tolerate medical therapies, including hypotension
  • Diuretic refractory
  • Inotropic support
  • Pulmonary hypertension and right heart failure
  • Six-minute walk test <300m
  • Increased 1yr mortality >20%
  • Renal or hepatic dysfunction
  • Chronic hyponatremia <134 chronically
  • Cardiac cachexia
  • Unable to tolerate ADLs

HFpEF

• Manage risk factors:
  • Treat hypertension
  • Treat atrial fibrillation
• SGLT2 inhibitors decrease hospitalizations and cardiovascular mortality
• In some patients with LVEF at the lower end: mineralocorticoid agonists and ARBs (or even ARNi)
• Diuretics as needed

Prognosis

• 30-40% of patients die within 1 year of diagnosis and 60-70% die within 5 years
• NYHA II have a 5-10% annual mortality rate
• NYHA IV have a 30-70% annual mortality rate
• MAGGIC risk score
  • Estimates 1 and 3 year survival

Further Reading

• Harrison's 19e (Ch 234)
• AHA/ACC/HFSA Guidelines 2022
• Does this dyspneic patient in the emergency department have congestive heart failure? JAMA RCE 2005