Heart failure with reduced ejection fraction (HFrEF)

A 68 year old male with a history of hypertension, type 2 diabetes mellitus, and coronary artery disease presents with progressive shortness of breath over the past 2 weeks. He reports fatigue, orthopnea, paroxysmal nocturnal dyspnea, and bilateral lower extremity swelling, along with recent weight gain. On examination, he appears dyspneic with elevated jugular venous pressure, bilateral pitting edema, and diffuse crackles on lung auscultation. Cardiac examination reveals a displaced apical impulse and an S3 gallop. Chest X-ray shows cardiomegaly, pulmonary congestion, and bilateral pleural effusions. Laboratory evaluation reveals elevated BNP and NT-proBNP, worsening renal function, and hyponatremia. Echocardiography demonstrates a dilated left ventricle, global hypokinesis, and LVEF 35 percent. Diagnosis?

Diagnosis is acute decompensated heart failure with reduced ejection fraction (HFrEF), likely secondary to ischemic cardiomyopathy.

1. Definition

Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome characterized by:

1. Symptoms and/or signs of heart failure
2. Left ventricular ejection fraction ≤40 percent
3. Often supported by elevated natriuretic peptides or objective evidence of structural heart disease

It results from impaired myocardial contractility, leading to reduced cardiac output, elevated filling pressures, and neurohormonal activation.

2. Etiology

2.1 Ischemic

1. Coronary artery disease
2. Prior myocardial infarction

2.2 Non-ischemic

1. Dilated cardiomyopathy
2. Myocarditis
3. Alcohol or cocaine toxicity
4. Chemotherapy-induced cardiomyopathy
5. Peripartum cardiomyopathy

2.3 Pressure or Volume Overload

1. Chronic hypertension
2. Aortic stenosis
3. Mitral or aortic regurgitation

2.4 Tachycardia-induced

1. Atrial fibrillation
2. Supraventricular tachycardia

2.5 Infiltrative and Metabolic

1. Amyloidosis
2. Hemochromatosis
3. Sarcoidosis

3. Pathophysiology

3.1 Core Mechanism

1. Reduced contractility → decreased stroke volume
2. Decreased cardiac output → hypoperfusion

3.2 Neurohormonal Activation

1. RAAS activation → vasoconstriction and sodium retention
2. Sympathetic activation → increased heart rate and oxygen demand
3. ADH release → water retention and hyponatremia

3.3 Ventricular Remodeling

1. Left ventricular dilation with eccentric hypertrophy
2. Increased wall stress
3. Fibrosis and myocyte loss

3.4 Hemodynamic Consequences

1. Increased LV end-diastolic pressure → pulmonary congestion
2. Increased right-sided pressures → systemic congestion
3. Reduced renal perfusion → worsening renal function

3.5 Vicious Cycle

Low cardiac output → neurohormonal activation → remodeling → further decline in ejection fraction

4. Hemodynamic Profile

1. Decreased cardiac output and cardiac index
2. Increased LV end-diastolic pressure
3. Increased pulmonary capillary wedge pressure (>18 mm Hg)
4. Increased systemic vascular resistance
5. Increased right atrial pressure

5. Classification

5.1 By Ejection Fraction

1. HFrEF ≤40 percent
2. HFmrEF 41–49 percent
3. HFpEF ≥50 percent

5.2 NYHA Functional Classification

1. Class I: No limitation
2. Class II: Mild limitation
3. Class III: Marked limitation
4. Class IV: Symptoms at rest

5.3 ACC/AHA Staging

1. Stage A: At risk
2. Stage B: Structural disease without symptoms
3. Stage C: Symptomatic heart failure
4. Stage D: Refractory heart failure

6. Clinical Features

6.1 Symptoms

1. Dyspnea
2. Orthopnea
3. Paroxysmal nocturnal dyspnea
4. Fatigue
5. Peripheral edema
6. Weight gain
7. Early satiety

6.2 Signs

1. Elevated jugular venous pressure
2. S3 gallop
3. Pulmonary crackles
4. Displaced apical impulse
5. Peripheral edema

6.3 Advanced Features

1. Hypotension
2. Cold extremities
3. Cardiorenal syndrome

7. Diagnosis

7.1 Laboratory

1. Elevated BNP or NT-proBNP
2. Age-adjusted NT-proBNP thresholds may support diagnosis

1.  >450 pg/mL if <50 years

2. >900 pg/mL if 50–75 years

3. >1800 pg/mL if >75 years

3. Hyponatremia indicates severe disease
4. Elevated creatinine indicates renal involvement

7.2 Imaging

1. Chest X-ray shows cardiomegaly, pulmonary edema, and pleural effusions

7.3 ECG

1. Left ventricular hypertrophy
2. Q waves
3. Left bundle branch block
4. Arrhythmias

7.4 Echocardiography

1. LVEF ≤40 percent
2. Dilated left ventricle
3. Hypokinesis
4. Valvular abnormalities

7.5 Advanced Evaluation

1. Cardiac MRI for infiltrative or inflammatory disease
2. Coronary angiography for ischemic evaluation
3. Right heart catheterization for hemodynamic assessment

8. Management

8.1 Guideline-Directed Medical Therapy

1. ARNI preferred or ACE inhibitor or ARB
2. Evidence-based beta blockers (metoprolol succinate, carvedilol, bisoprolol)
3. Mineralocorticoid receptor antagonists
4. SGLT2 inhibitors

8.2 Symptom Relief

1. Loop diuretics for volume overload
2. Add thiazide diuretics if resistant

8.3 Additional Therapies

1. Hydralazine plus isosorbide dinitrate in selected patients
2. Ivabradine if heart rate ≥70 in sinus rhythm
3. Digoxin reduces hospitalization
4. Intravenous iron in iron deficiency
5. Anticoagulation in atrial fibrillation

8.4 Device Therapy

1. ICD indicated if:
• LVEF ≤35 percent
• On optimal medical therapy for ≥3 months
• Life expectancy >1 year
2. CRT indicated if:
• LVEF ≤35 percent
• Sinus rhythm
• LBBB with QRS ≥150 ms
• Persistent symptoms despite GDMT

9. Acute Decompensated Heart Failure

1. Oxygen or noninvasive ventilation if hypoxic
2. Intravenous loop diuretics are first line
3. Vasodilators such as nitroglycerin in hypertensive patients
4. Inotropes for hypoperfusion or cardiogenic shock

10. Prognosis and Monitoring

1. Prognosis is variable and depends on disease severity
2. Poor prognostic factors:
• Low ejection fraction
• Elevated BNP
• Renal dysfunction
• Hyponatremia
3. Monitor renal function and electrolytes regularly
4. Repeat echocardiography after clinical change or therapy optimization

11. Key Clinical Insight

Dyspnea + orthopnea + S3 gallop + LVEF ≤40 percent = HFrEF

Congestion versus hypoperfusion guides management

12. Exam Level Pearls

1. Four pillar therapy reduces mortality and hospitalizations
2. S3 gallop indicates systolic dysfunction
3. BNP supports diagnosis
4. Do not discontinue GDMT even if ejection fraction improves
5. LVEF ≤35 percent indicates need for ICD evaluation
6. LBBB with wide QRS indicates benefit from CRT
7. IV loop diuretics are first line in acute decompensation

Aortic Stenosis

A 72 year old male presents with progressive exertional dyspnea, episodes of chest pain, and a recent episode of syncope while climbing stairs. He has a history of hypertension and hyperlipidemia. On examination, his pulse is low amplitude and delayed. Blood pressure is 130/85 mm Hg. Cardiac auscultation reveals a harsh crescendo–decrescendo systolic ejection murmur best heard at the right upper sternal border, radiating to the carotids. The second heart sound is soft, and an S4 gallop is present. Echocardiography shows aortic valve area of 0.8 cm², peak velocity of 4.5 m/s, and mean gradient of 50 mmHg, with preserved LVEF. Diagnosis?

Diagnosis is Symptomatic Severe Aortic Stenosis.

1. Definition

Aortic stenosis is a valvular disorder characterized by progressive narrowing of the aortic valve, resulting in obstruction to left ventricular outflow, causing pressure overload, concentric left ventricular hypertrophy, and eventual heart failure.

2. Etiology

1. Degenerative calcific AS (most common in elderly)
• Progressive leaflet calcification and reduced mobility
• Risk factors overlap with atherosclerosis
2. Bicuspid aortic valve
• Congenital abnormality leading to early calcification
• Presents earlier, often in middle age
3. Rheumatic heart disease
• Commissural fusion, often with concomitant mitral disease

3. Pathophysiology

1. Fixed obstruction increases afterload → concentric LV hypertrophy
2. LVH leads to:
• Increased oxygen demand
• Reduced subendocardial perfusion
3. Results in myocardial ischemia even without CAD
4. Diastolic dysfunction develops due to stiff ventricle
5. Advanced disease leads to:
• Reduced stroke volume
• Decreased cardiac output
• Pulmonary congestion and heart failure

4. Clinical Features

4.1 Classic Triad

1. Angina
• Due to supply-demand mismatch
2. Dyspnea
• Due to elevated LV filling pressures
3. Syncope (exertional)
• Due to inability to augment cardiac output during vasodilation

4.2 Additional Features

1. Fatigue and reduced exercise tolerance
2. Presyncope or dizziness
3. Signs of heart failure in advanced disease

5. Special Association

Heyde Syndrome

1. Aortic stenosis + GI bleeding from angiodysplasia
2. Mechanism:
• High shear stress across valve → degradation of von Willebrand factor
• Leads to acquired bleeding tendency

6. Physical Examination

1. Murmur
• Harsh crescendo–decrescendo systolic murmur
• Best heard at right upper sternal border
• Radiates to carotids
• May radiate to apex
2. Carotid pulse
• Pulsus parvus et tardus
3. Heart sounds
• Soft or absent A2
• Paradoxical splitting of S2
• S4 gallop
4. Pulse pressure
• Often narrow
5. Dynamic maneuvers
• Increases with squatting
• Decreases with Valsalva

7. Diagnosis

7.1 Transthoracic Echocardiography (Gold Standard)

Evaluates:

1. Valve anatomy and calcification
2. Aortic valve area (AVA)
3. Peak velocity
4. Mean gradient
5. Left ventricular function

Severity must be assessed using multiple parameters.

7.2 Additional Investigations

1. ECG
• LVH, left atrial enlargement
2. Chest X-ray
• LV enlargement
• Aortic valve calcification
• Post-stenotic dilation
3. Cardiac catheterization
• Used when noninvasive data are discordant
• Required before intervention

8. Severity Classification

Severity	AVA (cm²)	Velocity (m/s)	Gradient (mmHg)
Mild	>1.5	<3	<20
Moderate	1.0–1.5	3–4	20–40
Severe	≤1.0	≥4	≥40

9. Hemodynamic Subtypes

9.1 Classical Low-Flow Low-Gradient

• LVEF <50%
• Reduced stroke volume
• Requires dobutamine stress echo

9.2 Paradoxical Low-Flow Low-Gradient

• LVEF ≥50%
• Small, stiff LV
• Reduced stroke volume

9.3 Normal-Flow Low-Gradient

• Discordant findings
• Requires careful reassessment

10. Management

10.1 Medical Therapy

1. Symptomatic relief only
2. Diuretics for congestion, used cautiously
3. Treat hypertension carefully, including ACE inhibitors or ARBs
4. Maintain adequate preload

Medical therapy does not halt disease progression.

10.2 Definitive Treatment

Valve replacement is the only curative therapy

SAVR

• Preferred in younger patients
• Bicuspid valve
• Concomitant surgery needed

TAVR

• Preferred in older patients or high-risk individuals
• Decision based on age, anatomy, and comorbidities

11. Indications for Valve Replacement

1. Symptomatic severe AS
2. Severe AS with LVEF <50%
3. Selected asymptomatic patients with:
• Very severe AS
• Abnormal exercise test
• Rapid progression
• Elevated BNP

12. Complications

1. Heart failure
2. Arrhythmias
3. Sudden cardiac death
4. Pulmonary hypertension

13. Prognosis

1. Long asymptomatic phase
2. Once symptoms develop:
• Angina → ~5 year survival
• Syncope → ~3 year survival
• Heart failure → ~2 year survival

14. Key Clinical Insight

Aortic stenosis should be suspected in elderly patients with exertional syncope, angina, or dyspnea and a systolic murmur radiating to the carotids. Once symptoms develop, mortality increases sharply without valve replacement, making early recognition and timely intervention critical.

Triad of angina, syncope, and dyspnea = symptomatic severe aortic stenosis → urgent valve replacement

15. Exam Pearls

1. Triad: angina, syncope, dyspnea
2. Murmur radiates to carotids
3. Pulsus parvus et tardus is hallmark
4. Echo is diagnostic
5. Low-flow low-gradient AS requires careful evaluation
6. Valve replacement is definitive treatment
7. Do not delay intervention once symptoms appear

Inferior Wall STEMI

A 50 year old male presents to the emergency department with acute onset substernal chest pain, diaphoresis, and vomiting for the past 30 minutes. He has a history of hypertension, diabetes mellitus, and hyperlipidemia, and is noncompliant with medications. He is an active smoker. On examination, blood pressure is 90/60 mm Hg, pulse rate is 58 beats per minute, and respiratory rate is 18 breaths per minute. Jugular venous pressure is elevated. Electrocardiography shows sinus bradycardia with ST-segment elevation in leads II, III, and aVF, with reciprocal ST depression in leads I and aVL. Cardiac troponins are elevated, although treatment should not be delayed while awaiting results. Echocardiography shows inferior wall hypokinesis. Diagnosis?

Diagnosis is Inferior Wall ST Elevation Myocardial Infarction (STEMI), most likely due to right coronary artery occlusion, with suspected right ventricular infarction.

1. Definition

Inferior wall myocardial infarction is an acute ischemic injury involving the inferior wall of the left ventricle, most commonly due to right coronary artery occlusion in right-dominant circulation, and less commonly due to left circumflex artery occlusion in left-dominant anatomy.

2. Epidemiology and Risk Factors

2.1 Epidemiology

1. Accounts for 40 to 50 percent of all myocardial infarctions
2. Generally has a better prognosis than anterior MI
3. Right ventricular involvement occurs in up to 40 percent of cases and worsens outcomes

2.2 Risk Factors

1. Hypertension
2. Diabetes mellitus
3. Hyperlipidemia
4. Smoking
5. Obesity and sedentary lifestyle
6. Advanced age and family history

3. Pathophysiology

3.1 Core Mechanism

1. Atherosclerotic plaque rupture leads to platelet activation and thrombus formation
2. Results in acute coronary occlusion, causing myocardial ischemia and necrosis

3.2 Coronary Anatomy

1. Right coronary artery supplies the inferior wall, right ventricle, and often the SA and AV nodes
2. In left-dominant circulation, the LCx supplies the inferior wall

3.3 Conduction Abnormalities

1. Sinus bradycardia is common in early inferior MI
2. AV nodal block, especially Mobitz type I, is frequent
3. High-grade AV block may occur and requires urgent management

3.4 Bezold–Jarisch Reflex

1. Causes bradycardia, hypotension, and vasodilation
2. Triggered by inferior wall ischemia and vagal activation

4. Clinical Features

4.1 Core Symptoms

1. Chest pain, often radiating to arm or jaw
2. Diaphoresis
3. Nausea and vomiting

4.2 Inferior MI Specific Features

1. Bradycardia due to vagal tone and nodal ischemia
2. Hypotension with elevated JVP, suggesting right ventricular infarction
3. Relative absence of pulmonary edema in isolated RV infarction

5. ECG Findings

1. ST-segment elevation in leads II, III, and aVF
2. Reciprocal ST depression in leads I and aVL
3. ST elevation in lead III greater than lead II suggests RCA involvement
4. Right-sided leads (V4R) should be obtained to evaluate for right ventricular infarction

6. Diagnostic Evaluation

6.1 Electrocardiography

1. Initial test of choice
2. Should be performed immediately

6.2 Cardiac Biomarkers

1. Troponins are elevated
2. Diagnosis of STEMI is ECG-based, and treatment should not be delayed

6.3 Echocardiography

1. Shows inferior wall motion abnormalities
2. Helps detect right ventricular involvement and complications

6.4 Coronary Angiography

1. Confirms the culprit vessel
2. Enables primary PCI, the definitive therapy

6.5 Laboratory Studies

1. CBC, metabolic panel, and coagulation profile prior to intervention

7. Key Clinical Insight

Inferior STEMI with hypotension, elevated JVP, and bradycardia strongly suggests right ventricular infarction due to proximal RCA occlusion.

8. Management

8.1 Reperfusion Therapy

1. Primary PCI within 90 minutes is preferred
2. Thrombolysis if PCI cannot be performed within 120 minutes

8.2 Antithrombotic Therapy

1. Aspirin 162 to 325 mg
2. P2Y12 inhibitor such as clopidogrel or prasugrel
3. Anticoagulation with unfractionated heparin or alternatives

8.3 Hemodynamic Management

1. Intravenous crystalloids for hypotension due to RV infarction
2. Avoid nitrates and diuretics in RV infarction due to preload dependence
3. Norepinephrine is the preferred vasopressor if hypotension persists

8.4 Bradyarrhythmia Management

1. Atropine for symptomatic bradycardia
2. Temporary transvenous pacing if high-grade AV block persists

8.5 Adjunct Therapy

1. High-intensity statins
2. ACE inhibitors or ARBs
3. Beta blockers only if no hypotension, bradycardia, AV block, or RV infarction

8.6 Secondary Prevention

1. Smoking cessation
2. Control of blood pressure, lipids, and glucose
3. Cardiac rehabilitation

9. Complications

1. Bradyarrhythmias and AV nodal block
2. Right ventricular failure
3. Cardiogenic shock
4. Ventricular tachycardia or ventricular fibrillation

10. Prognosis

1. Better prognosis than anterior MI
2. Mortality approximately 2 to 9 percent
3. Worse outcomes with right ventricular involvement, delayed reperfusion, or conduction abnormalities

11. Exam Level Pearls

1. ST elevation in II, III, and aVF indicates inferior MI
2. ST elevation in lead III greater than lead II suggests RCA occlusion
3. Hypotension with elevated JVP indicates right ventricular infarction
4. Avoid nitrates in RV infarction
5. Inferior MI commonly causes bradycardia and AV block
6. Obtain right-sided ECG leads when RV infarction is suspected