Heart Failure Study Note

Definition and Core Pathophysiology

Heart failure is a clinical syndrome with symptoms and/or signs caused by structural and/or functional cardiac abnormality, corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. 1, 2, 3

The syndrome results from the heart's inability to pump and/or fill with blood adequately, leading to inadequate cardiac output or requiring compensatory neurohormonal activation with increased left ventricular filling pressures 2, 4
Most patients experience dyspnea and fatigue from impaired left ventricular function, plus fluid retention causing pulmonary congestion and peripheral edema 2, 4
The condition affects more than 64 million people worldwide, representing a global pandemic with substantial geographical variations 1, 2

Classification by Left Ventricular Ejection Fraction (LVEF)

The 2022 ACC/AHA/HFSA guidelines establish four distinct categories based on LVEF trajectories: 1, 3

Primary Categories

HFrEF (Heart Failure with Reduced EF): LVEF ≤40% 1, 3
HFmrEF (Heart Failure with Mildly Reduced EF): LVEF 41-49% 1, 3
HFpEF (Heart Failure with Preserved EF): LVEF ≥50% 1, 3
HFimpEF (Heart Failure with Improved EF): Previous LVEF ≤40% with follow-up measurement >40% 1, 3

Critical Clinical Pearls

Patients with HFimpEF should continue HFrEF treatment even after LVEF improves to >40%, as EF improvement does not mean full myocardial recovery and withdrawal of therapy often leads to EF decline 1
Cardiac structural abnormalities (LV chamber dilatation, systolic/diastolic dysfunction) typically persist despite LVEF improvement 1
LVEF trajectory is prognostically important—significant reduction over time indicates poor prognosis 1

Diagnostic Criteria for HFmrEF and HFpEF

Both HFmrEF and HFpEF require evidence of elevated LV filling pressures at rest, exercise, or provocation in addition to appropriate LVEF range: 1

Required Evidence (Any One of the Following)

Elevated natriuretic peptides: BNP >35 pg/mL and/or NT-proBNP >125 pg/mL 1
Echocardiographic diastolic parameters: E/e' ≥15 or other evidence of elevated filling pressures 1
Invasive hemodynamic measurement at rest or exercise demonstrating elevated filling pressures 1

Supportive Structural Evidence

Increased left atrial size/volume (left atrial volume index) 1
Increased LV mass (LV mass index) 1
LV hypertrophy or left atrial enlargement 1

Epidemiology and Demographics

HFpEF represents approximately 50% of all heart failure cases worldwide, making it the most common type. 1, 5

Age and Sex Distribution

HFpEF is more common in people over 75 years old, with significant prevalence increase after this age 5
HFpEF predominates in women, while HFrEF is more common in younger men 5
HFrEF affects approximately 50% of the 64 million people with heart failure globally 6

Geographic Variations in HF Subtypes

ESC-HF-LT registry (Europe): 60% HFrEF, 24% HFmrEF, 16% HFpEF 5
GWTG-HF registry (United States): 39% HFrEF, 14% HFmrEF, 47% HFpEF 5
G-CHF registry (Global): 54% HFrEF, 24% HFmrEF, 21% HFpEF 5

Risk Factors

Patients with hypertension and diabetes are at higher risk of developing HFpEF 5
Prevalence is increasing due to aging population, improved survival with ischemic heart disease, and effective evidence-based therapies prolonging life 1

ACC/AHA Staging System

The staging system reflects progressive disease that typically advances forward without reversal, even when symptoms improve with treatment: 1, 2

Stage A: At Risk for Heart Failure

Patients with hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, cardiotoxin use, or family history of cardiomyopathy 1
No structural heart disease or symptoms of HF 1
Management: Reduce modifiable risk factors, manage hypertension and hyperlipidemia 2

Stage B: Pre-Heart Failure

Structural heart disease without signs or symptoms of HF 1
Includes LV remodeling, LV hypertrophy, asymptomatic valvular disease, previous MI 1
Management: ACE inhibitors and beta-blockers in all patients with reduced EF to prevent symptomatic HF 2

Stage C: Symptomatic Heart Failure

Structural heart disease with prior or current symptoms of HF 1
Marked symptoms despite maximal medical therapy, shortness of breath and fatigue 1
Management: Diuretics for fluid retention plus ACE inhibitors and beta-blockers 2

Stage D: Advanced Heart Failure

Refractory HF requiring specialized interventions 1, 3
Severe symptoms at rest, recurrent hospitalizations despite guideline-directed management 3
Requires consideration for transplant, mechanical circulatory support, or palliative care 3

NYHA Functional Classification

The NYHA system assesses current symptom severity and exercise intolerance, correlating poorly with LV function measures but strongly with survival: 1, 2

Class I: No limitation of physical activity; ordinary activity does not cause symptoms 1
Class II: Slight limitation of physical activity; comfortable at rest but ordinary activity causes symptoms 1
Class III: Marked limitation of physical activity; comfortable at rest but less than ordinary activity causes symptoms 1
Class IV: Unable to carry out any physical activity without symptoms; symptoms present at rest 1

Key Distinction from ACC/AHA Staging

NYHA classification reflects current functional status and can change frequently with treatment 2
ACC/AHA staging reflects disease progression and typically does not reverse 2
The two systems are complementary and should be used together 2

Acute Heart Failure Classifications

Killip Classification (Post-MI Setting)

Developed for acute myocardial infarction patients, classifying severity based on clinical findings: 1

Class I: No clinical signs of cardiac decompensation (mortality 2.2%) 1
Class II: Rales, S3 gallop, pulmonary venous hypertension—wet rales in lower half of lung fields (mortality 10.1%) 1
Class III: Frank pulmonary edema with rales throughout lung fields (mortality 22.4%) 1
Class IV: Cardiogenic shock—SBP <90 mmHg with peripheral vasoconstriction, oliguria, cyanosis, diaphoresis (mortality 55.5%) 1

Forrester Classification (Hemodynamic)

Classifies patients based on peripheral perfusion and pulmonary congestion: 1

Uses cardiac index (CI) threshold of 2.2 L/min/m² and pulmonary capillary wedge pressure (PCWP) threshold of 18 mmHg 1
Clinical assessment includes filliform pulse, cold clammy skin, peripheral cyanosis for hypoperfusion 1
Hemodynamic assessment provides objective CI and PCWP measurements 1

Acute Coronary Syndrome with Heart Failure (ACS-HF)

ACS-HF occurs in 11-25% of patients presenting with acute coronary syndrome, with significantly elevated mortality: 1

Risk Factors for ACS-HF

Age: OR 1.3 for every 5-10 year increase 1
Female sex: Approximately 10% higher incidence than males 1
Preexisting HF or LVSD: Up to 4-fold higher risk of decompensation after MI or ACS 1
Type 2 diabetes: OR 1.23-2.3 for ACS-HF 1
Atrial fibrillation, hypertension, chronic kidney disease: Consistently associated with increased risk 1

Mortality Impact

In-hospital mortality: 12% with ACS-HF vs 2.9% without (p<0.0001) 1
6-month mortality: 20.7% with ACS-HF vs 5.9% without (p<0.0001) 1
Adjusted risk at 1 year: OR 2.1 (95% CI: 1.70-2.60) 1

High-Output Heart Failure

A distinct syndrome where patients exhibit typical HF symptoms despite elevated cardiac output >8 L/min or cardiac index >4 L/min/m², caused by conditions lowering systemic vascular resistance or creating arteriovenous shunts rather than primary myocardial disease. 7

Common Etiologies

Liver disease/cirrhosis: Accounts for approximately 23% of cases 7
Arteriovenous shunts/fistulas (including dialysis access): Approximately 23% of cases 7
Severe chronic anemia: Frequent precipitant 7
Thyrotoxicosis/hyperthyroidism: Can raise cardiac output up to 300% of baseline 7
Septicemia, Paget's disease of bone, Beri-beri (thiamine deficiency): Less common causes 7

Distinguishing Clinical Features

Warm, bounding pulses with warm extremities—contrasts with cool extremities of low-output cardiogenic shock 7
Tachycardia, elevated jugular venous pressure, pulmonary congestion, peripheral edema 7
Echocardiography shows four-chamber cardiac enlargement and increased LV outflow tract velocity-time integral 7

Diagnostic Work-up

Thyroid function testing for thyrotoxicosis 7
Complete blood count for anemia 7
Liver function tests for cirrhosis 7
Vascular imaging (Doppler ultrasound, CT angiography) for arteriovenous malformations or fistulas 7

Management Approach

Primary treatment is addressing the underlying cause: correcting anemia, treating thyrotoxicosis, closing arteriovenous fistulas, managing liver disease 7
Dietary sodium and water restriction with judicious diuretic use for fluid overload 7

Prognosis and Economic Burden

Heart failure carries worse prognosis than certain common cancers, with 5-year survival rate of 25% after hospitalization for HFrEF. 6

Mortality and Morbidity

Symptom severity correlates poorly with LV function measures but strongly with survival 1
Patients with mild symptoms still have increased risk of hospitalization and death 1
The economic burden and morbidity of HFpEF are comparable to or greater than HFrEF, with similar hospitalization and mortality rates 5

Economic Impact

Total cost in USA estimated at $30.7 billion in 2012 1
Projected to increase by 127% to $69.8 billion by 2030, approximately $244 per US adult 1, 2
In Europe, prevalence ranges from 1-2.3% of general population 2

Exercise Rehabilitation

Exercise cardiac rehabilitation (ExCR) provides significant benefits across multiple outcomes in heart failure patients: 1

Quality of Life and Exercise Capacity Benefits

Overall improvement in health-related quality of life with standardized score coefficient 0.26 (95% CI: 0.12-0.40) 1
Peak VO2 improvement overall coefficient -5.94 (95% CI: -10.9 to -1.01) 1
6-minute walk test improvement 21.0 meters (95% CI: 1.57-40.4) at 12 months 1

Subgroup Considerations

Benefits observed across both HFrEF and HFpEF populations 1
NYHA Class III patients showed greater peak VO2 improvement (-10.2 ml/kg/min) compared to Class II (-3.95 ml/kg/min), though interaction p=0.061 1
No significant differences in benefit by age, sex, heart failure etiology, or baseline peak VO2 1

Common Pitfalls and Clinical Pearls

Diagnostic Pitfalls

Do not assume normal LVEF excludes heart failure—HFpEF requires additional evidence of elevated filling pressures beyond LVEF ≥50% 1
Do not discontinue HFrEF therapy when LVEF improves to >40%—these HFimpEF patients need continued treatment to prevent EF decline 1
Do not rely solely on symptoms to assess severity—symptom severity correlates poorly with LV function measures 1

Management Pitfalls

Do not treat HFpEF and HFrEF identically—HFpEF has recently shown benefit with SGLT2 inhibitors but lacks the extensive disease-modifying therapies proven for HFrEF 1, 5
Do not overlook high-output heart failure—look for warm extremities and underlying causes (thyroid, anemia, liver disease, AV fistulas) as primary treatment targets the etiology 7
Do not underestimate ACS-HF mortality risk—in-hospital mortality is 4-fold higher (12% vs 2.9%) and requires aggressive management 1

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