CARDIO Flashcards
Oxygen Consumption Rate
CO X (arterial O2 content − venous O2 content)
Can either be measured using a spirometer or by using an assumed value (usually 250 mL O2/min (or 3.5–4.0 mL/kg/min).
↑ Pulse Pressure
Hyperthyroidism
Aortic regurgitation
Aortic stiffening (isolated systolic hypertension in elderly)
Obstructive sleep apnea (↑ sympathetic tone)
Anemia
Exercise (transient)
↓ Pulse Pressure
Aortic stenosis
Cardiogenic shock
Cardiac tamponade
Advanced HF
Loud S1
Mitral stenosis (increased transvalvular pressure gradient)
Tachycardia (short diastole)
Hyperdynamic states (e.g., left-to-right shunts [increased transvalvular blood flow])
Short PR interval (e.g., atrioventricular reentrant tachycardia (AVRT))
S1 is generally not heard in aortic and pulmonary areas. It is considered “loud” if it is as loud as S2 in aortic and pulmonary areas.
Soft S1
Severe mitral stenosis (mitral valves are severely calcified and immobile)
Conditions that impair the transmission of heart sounds to the chest wall → COPD, pneumothorax, pericardial effusion, obesity
Left bundle branch block (LBBB) (delayed onset of systole)
Prolonged PR interval (e.g., first-degree heart blocks)
S1 is considered “soft” if S2 is louder than S1 at the mitral region.
S1 with Variable Intensity
Atrial fibrillation
AV dissociation
Auscultatory alternans → severe LV failure, large pericardial effusion
Loud A2
Arterial hypertension
Coarctation of the aorta
Loud P2
Pulmonary hypertension
Atrial septal defects
P2 is a soft sound and is usually heard only in the pulmonary area; therefore, P2 is considered “loud” when it is clearly heard in the mitral area or when it is louder than A2. A loud P2 is highly specific for pulmonary hypertension.
Signs of ↑ Jugular Venous Pressure (JVP)
Jugular venous distention
Kussmaul sign → distention of the jugular veins during inspiration due to the negative intrathoracic pressure that attempts to pull blood into the right heart, which is restricted by noncompliant pericardium or myocardium (e.g., constrictive pericarditis, restrictive cardiomyopathy, right atrial tumors, ventricular tumors, right HF, massive PE)
Hepatojugular reflux
Causes of ↑ Jugular Venous Pressure (JVP)
Right heart failure Fluid overload Tricuspid valve dysfunction Pericardial effusion Constrictive pericarditis Cardiac tamponade SVC syndrome Pulmonary hypertension
Kussmaul Sign
Distention of the jugular veins (↑ JVP) during inspiration due to the negative intrathoracic pressure that attempts to pull blood into the right heart, which is restricted by noncompliant pericardium or myocardium (e.g., constrictive pericarditis, restrictive cardiomyopathy, right atrial tumors, ventricular tumors, right HF, massive PE)
Kussmaul sign is absent during pericardial tamponade because the negative intrathoracic pressure is still able to ensure filling of the right ventricle.
JVP a wave
First peak caused by atrial contraction
Absent in atrial fibrillation
Prominent in tricuspid valve atresia
JVP c wave
Second peak caused by tricuspid valve closure, contraction of the right ventricle, and bulging of the tricuspid valve into the right atrium
cv wave (merging of the c and v waves; Lancisi sign) → severe tricuspid valve regurgitation
JVP x descent
A drop in JVP caused by atrial relaxation
Absent in:
- Tricuspid valve regurgitation
- Right heart failure
JVP v wave
The third peak caused by venous refilling of the right atrium against the closed tricuspid valve
Prominent in:
- Tricuspid valve regurgitation
- Right heart failure
JVP y descent
A drop in JVP caused by decreased right atrial pressure as blood flows into the right ventricle after opening of the tricuspid valve
The y descent is sharp and deep due to rapid filling in the first half of diastole.
Prominent in:
- Tricuspid valve regurgitation
- Constrictive pericarditis
Absent in:
- Cardiac tamponade
- Tricuspid valve stenosis
Third Heart Sound (S3)
- Early diastolic sound that is heard immediately after S2
- Ventricular gallop → S1 is followed by S2 and S3 in close succession, resembling the cadence of the word “Kentucky” (Ken-TUC-ky) on auscultation. Described as a ventricular gallop because the pattern of S1-S2-S3 on auscultation resembles the sound of a galloping horse.
- Occurrence:
1. Physiological → young individuals (< 40 years of age), athletes, or pregnant women
2. Pathological: - Chronic mitral regurgitation
- Aortic regurgitation
- Heart failure (due to dilated ventricles)
- Dilated cardiomyopathy
- Thyrotoxicosis
- L → R shunt
Fourth Heart Sound (S4)
- The fourth heart sound is often called an atrial gallop because the sound originates in the atria
- S1 rapidly follows S4, resembling the cadence of the word “Tennessee” (Ten-nes-SEE) on auscultation.
Occurrence:
- Physiological → advanced age (due to reduce ventricular compliance)
- Pathological if palpable
- Ventricular hypertrophy (e.g., hypertension, aortic stenosis, cor pulmonale)
- Ischemic cardiomyopathy
- Acute myocardial infarction
Split S1
Occurs when the closure of the tricuspid valve is delayed (e.g., due to an RBBB), resulting in the sound of tricuspid valve closure heard shortly after mitral valve closure Reversed splitting (tricuspid valve closure before mitral valve closure) is rare.
Causes:
Conduction disorders
Hemodynamic cause
S2 Physiological Split
The sound of aortic valve closure (A2) precedes the sound of pulmonary valve closure (P2) during inspiration
Inspiration → fall in intrathoracic pressure → increase in venous return to the right side of the heart → prolonged right ventricular systole → delayed closure of P2
Pooling of blood in pulmonary circulation → shortened left ventricular systole → premature A2
Especially pronounced among young individuals (chest wall excursion and, therefore, the likelihood of hearing a physiological split decreases with age)
S2 Wide Split
An exaggerated physiological split, which is more pronounced during inspiration (A2 precedes P2)
Caused by any condition that increases right ventricular afterload or decreases left ventricular preload
Increased right ventricular afterload → prolonged right ventricular systole
Decreased left ventricular preload → shortened left ventricular systole
Causes: Pulmonary hypertension Pulmonary valve stenosis RBBB Massive pulmonary embolism Severe mitral regurgitation Wolff-Parkinson-White syndrome Constrictive pericarditis
S2 Fixed Split
Does not change with respiration and tends to be wide, i.e., the split is also audible during expiration (since the right and left sides of the heart communicate, the pressure difference that normally exists during respiration evens out; therefore, the duration of the split does not change with inspiration or expiration)
Left-to-right shunt in ASD → RV volume overload → delay in the closure of the pulmonary valve
Cause:
Atrial septal defect (ASD)
Severe RV failure
S2 Paradoxical Split (Reversed Split)
Audible during expiration but not inspiration
Expiration → A2 is heard after P2 during expiration due to delayed closure of the aortic valve (split reversal)
Inspiration → the closure of the pulmonary valve is also delayed, resulting in A2 and P2 occurring simultaneously (i.e., a paradoxical decrease in the split during inspiration)
Cause: Aortic stenosis Left bundle branch block HOCM (LV outflow tract obstruction) Early excitation of the right ventricle (e.g., RV pacing, Wolff-Parkinson-White syndrome)
S2 Absent split
No splitting of S2
Cause:
- Severe aortic stenosis (geriatric) (A2 is absent due to calcification and, in severe cases, immobility of the aortic valves)
- VSD with Eisenmenger syndrome (pediatric) (VSD results in communication between the left and right ventricles. They then essentially function as a single ventricle, leading to A2 and P2 occurring simultaneously, during both inspiration and expiration (fused A2-P2)).
Lancisi sign
A physical exam finding in patients with severe tricuspid regurgitation.
The V wave merges with the C wave, forming a prominent wave on jugular venous examination that can resemble the carotid-pulse wave of aortic regurgitation.
Erb point
Location → 3rd left parasternal intercostal space
The best overview of heart sounds and murmurs can be obtained at the Erb point.
Pathology:
- Diastolic murmurs → aortic regurgitation, pulmonic regurgitation
- Systolic murmurs → HOCM
Aortic area Auscultation
Location:
2nd right parasternal intercostal space
Pathology: Aortic stenosis Aortic regurgitation Coarctation of the aorta Flow murmur (eg, physiologic murmur)
Pulmonic area Auscultation
Location:
2nd left parasternal intercostal space
Pathology: Pulmonary stenosis Pulmonary regurgitation ASD Flow murmur
Mitral area Auscultation
Location:
5th left intercostal space in the midclavicular line
Pathology:
Mitral stenosis
Mitral regurgitation
Mitral valve prolapse (MVP)
Tricuspid area Auscultation
Location:
4th left parasternal intercostal space
Pathology:
Tricuspid stenosis
Tricuspid regurgitation
Aortic Ejection Click
- Opening of a stiff aortic valve (results from the abrupt stop of the valve leaflets upon opening)
- Heard best with the diaphragm of a stethoscope at the aortic region with the patient seated and leaning forward
- Timing → early systolic sound (immediately after S1)
- Etiology → aortic stenosis
Mitral Valve Prolapse Click
- Mitral valve prolapse into the left atria during systole
- Heard best with the diaphragm of a stethoscope at the mitral region with the patient in left lateral position (MVP click is a high-frequency sound)
- Timing → midsystolic sound (often accompanied by a holosystolic, uniform murmur of mitral regurgitation.)
- Etiology → mitral valve prolapse
Mitral Valve Opening Snap
- Opening of a stiff mitral valve
- Heard best with the bell of a stethoscope at the mitral region with the patient in a left lateral position (mitral valve opening snap is a high-pitched)
- Timing → early diastolic sound (immediately after S2)
- Etiology → mitral stenosis
Mechanical Valve Clicks
- S1 and S2 sound like clicks.
- Heard best with the diaphragm of a stethoscope
- Timing → coincides with a normal S1 and S2
- Etiology → prosthetic valve
Pericardial Friction Rub
- Scratching sound due to friction between the visceral and parietal pleura (similar to the sound made when walking on snow)
- Heard best over the left sternal border during expiration with the patient sitting upright and leaning forward
- Timing → systolic or diastolic sound
- Etiology → pericarditis
Pericardial Knock
- Sudden cessation of ventricular filling against a rigid pericardial sack
- Heard best at the left sternal border
- Timing → diastolic sound
- Etiology → constrictive pericarditis
Functional Heart Murmur (Physiological or Innocent)
- An ejection murmur due to increased or turbulent blood flow across normal aortic and/or pulmonary valves, e.g., due to a hyperdynamic circulation
- Most commonly occurs in children and young adults
- Cardiac pathology must be ruled out.
- Soft (grade < 3/6 without a thrill)
- Most commonly midsystolic or continuous
- Position change → position-dependent; varies in intensity or disappears
Pathological Murmur
- Caused by structural defects (valvular disease or heart defects)
- Typically grade > 3/6
- Thrill may be present
- Systolic, diastolic, or continuous
- Position change → rarely disappears
Functional (Physiological or Innocent) Systolic Murmurs
- Children
- Pregnancy
- During states of excitement or strenuous activity
- Anemia
- Fever, sepsis
- Thyrotoxicosis
- Beriberi
- Arteriovenous fistula
- Still murmur
Pathological Systolic Murmurs
- Aortic stenosis
- Pulmonary stenosis
- Mitral regurgitation
- Tricuspid regurgitation
- VSD
- Coarctation of the aorta
- HOCM
Still Murmur
- Most common innocent murmur in children (differential diagnosis includes a VSD, which is a harsh, loud, pansystolic murmur)
- Grade 1–3 midsystolic murmur heard best at the left midsternal border or between the left lower sternal border and the apex
- Louder when the patient is supine and softer when the patient is upright
- Unknown etiology
Functional (Physiological or Innocent) Continuous Murmur
Hyperdynamic state
Cervical venous hum
Pathological Continuous Murmur
PDA
Arteriovenous fistulas
Cervical Venous Hum
- Functional (Physiological or Innocent) Continuous Murmur
- Common benign finding in children due to turbulent flow in internal jugular veins
- Heard best at the infraclavicular and supraclavicular regions (more common on the right side)
- Becomes softer or disappears with flexion of the head, compression of the jugular vein, or in the supine position
- May radiate to the 1st and 2nd ICS (could be misdiagnosed as a PDA if it is heard on the left side)
Inspiration Maneuver
Effect on cardiac parameters:
- ↑ RV preload
- ↓ LV preload
- No effect on LV afterload
Effect on murmurs:
- ↑ Intensity of murmurs arising from the right side of the heart
- ↓ Intensity of murmurs arising from the left side of the heart
Opposite effect is achieved with expiration
Expiration Maneuver
Effect on cardiac parameters:
- ↑ LV preload
- ↓ RV preload
Effect on murmurs:
- ↑ Intensity of murmurs arising from the left side of the heart
- ↓ Intensity of murmurs arising from the right side of the heart
Opposite effect is achieved with inspiration
Valsalva Maneuver
Effect on cardiac parameters:
- ↓ RV preload
- ↓ LV preload
- ↓ LV afterload
Effect on murmurs:
- ↑ Intensity of MVP (with early midsystolic click) and hypertrophic cardiomyopathy (HCM) murmurs
- ↓ Intensity of murmurs arising from the left side of the heart
Opposite effect is achieved by squatting, lying down quickly or raising the legs
Abrupt Standing Maneuver
Effect on cardiac parameters:
- ↓ RV preload
- ↓ LV preload
- ↓ LV afterload
Effect on murmurs:
- ↑ Intensity of MVP (with early midsystolic click) and hypertrophic cardiomyopathy (HCM) murmurs
- ↓ Intensity of murmurs arising from the left side of the heart
Opposite effect is achieved by squatting, lying down quickly or raising the legs
Squatting Maneuver
Effect on cardiac parameters:
- ↑ RV preload
- ↑ LV preload
- No effect on LV afterload (afterload may increase with squatting)
Effect on murmurs:
- ↑ Intensity of all murmurs
- ↓ Intensity of MVP (with late midsystolic click) and HCM murmurs
- Tetralogy of Fallot: The severity of tet spells and the associated murmurs decrease with squatting.
- MVP: click occurs later in systole
Opposite effect is achieved by standing up suddenly
Lying Down Quickly Maneuver
Effect on cardiac parameters:
- ↑ RV preload
- ↑ LV preload
- No effect on LV afterload (afterload may increase with squatting)
Effect on murmurs:
- ↑ Intensity of all murmurs
- ↓ Intensity of MVP (with late midsystolic click) and HCM murmurs
- Tetralogy of Fallot: The severity of tet spells and the associated murmurs decrease with squatting.
- MVP: click occurs later in systole
Opposite effect is achieved by standing up suddenly
Raising the Legs Maneuver
Effect on cardiac parameters:
- ↑ RV preload
- ↑ LV preload
- No effect on LV afterload (afterload may increase with squatting)
Effect on murmurs:
- ↑ Intensity of all murmurs
- ↓ Intensity of MVP (with late midsystolic click) and HCM murmurs
- Tetralogy of Fallot: The severity of tet spells and the associated murmurs decrease with squatting.
- MVP: click occurs later in systole
Opposite effect is achieved by standing up suddenly
Hand grip Maneuver
Effect on cardiac parameters:
- No effect on RV preload
- No effect on LV preload
- ↑ LV afterload
Effect on murmurs:
- ↑ Intensity of murmurs resulting from backward flow of blood in the left side of the heart (e.g., aortic regurgitation, mitral regurgitation, VSD, MVP)
- ↓ Intensity of murmurs associated with forward flow of blood in the left side of the heart (e.g., mitral stenosis, aortic stenosis, HCM)
- MVP: click occurs later in systole
Opposite effect is achieved with the use of amyl nitrite (vasodilator)
Sitting and Leaning Forward Maneuver
Effect on cardiac parameters:
- No effect
Effect on murmurs:
- ↑ Intensity of murmurs at or near the aortic valve (e.g., aortic stenosis, aortic regurgitation, coarctation of the aorta, HOCM)
Lying Down in the Left Lateral Position Maneuver
Effect on cardiac parameters:
- No effect
Effect on murmurs:
- ↑ Intensity of murmurs at or near the mitral valve (e.g., mitral stenosis, mitral regurgitation, MVP)
Acute Aortic Regurgitation Etiology
- Infective endocarditis (most common valvular cause of acute aortic regurgitation)
- Aortic dissection (ascending aorta) (most common aortic cause of acute aortic regurgitation)
- Chest trauma
- Iatrogenic complications (e.g., after percutaneous aortic balloon dilation or transcatheter aortic valve replacement (TAVR))
Chronic Aortic Regurgitation Etiology
Primary valvular defect (aortic root dilation is often secondary in primary valvular defects)
- Congenital bicuspid aortic valve → most common cause of AR in young adults in high-income countries
- Calcific aortic valve disease → most common cause of AR in older patients in high-income countries (approximately 75% of patients with aortic valve stenosis also have some degree of aortic valve regurgitation)
- Rheumatic heart disease → most common cause of AR in lower-income countries
Aortic dilatation (can be caused by any disease or defect of the ascending aorta and/or the aortic root and does not always directly involve the aortic valve)
- Connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome)
- Chronic hypertension
- Aortitis of any etiology (e.g., tertiary syphilis)
- Thoracic aortic aneurysm
Acute Aortic Regurgitation Signs & Symptoms
- Sudden, severe dyspnea
- Rapid cardiac decompensation secondary to heart failure
- Pulmonary edema
- Symptoms related to underlying disease (e.g., fever due to endocarditis, chest pain due to aortic dissection)
- Soft S1 (due to elevated LV end-diastolic pressure leading to an early closure of the mitral valve)
- Soft and short early diastolic murmur
Findings specific to acute AR:
- Reduced cardiac output
- Elevated end-diastolic left ventricular pressure
- Early mitral valve closing (the sudden and massive volume increase in the left ventricle leads to an elevation in LV pressure, which then rapidly exceeds left atrial pressure, leading to the early closing of the mitral valve)
- Rapid equilibration of aortic and left ventricular pressure
- ECG shows possible signs of the underlying cause (e.g., signs of myocardial ischemia in aortic dissection)
- Chest x-ray shows normal heart silhouette and signs of pulmonary congestion or edema
Acute Aortic Regurgitation Findings
Auscultation
- Soft S1 (due to elevated LV end-diastolic pressure leading to an early closure of the mitral valve)
- Soft and short early diastolic murmur
Findings specific to acute AR:
- Reduced cardiac output
- Elevated end-diastolic left ventricular pressure
- Early mitral valve closing (the sudden and massive volume increase in the left ventricle leads to an elevation in LV pressure, which then rapidly exceeds left atrial pressure, leading to the early closing of the mitral valve)
- Rapid equilibration of aortic and left ventricular pressure
ECG shows possible signs of the underlying cause (e.g., signs of myocardial ischemia in aortic dissection)
Chest x-ray shows normal heart silhouette and signs of pulmonary congestion or edema
Chronic Aortic Regurgitation Sign & Symptoms
May be asymptomatic for up to decades despite progressive LV dilation
Palpitations
Symptoms of high pulse pressure
- Water hammer pulse of peripheral arteries characterized by rapid upstroke and downstroke
- Pulsing of carotid arteries with rapid upstroke and downstroke
- Quincke sign → visible capillary pulse when pressure is applied to the tip of a fingernail
- De Musset sign → rhythmic nodding or bobbing of the head in synchrony with heartbeats
Symptoms of left heart failure
- Exertional dyspnea
- Angina
- Orthopnea
- Easy fatigability
- Syncope
Point of maximal impulse (PMI) → diffuse, hyperdynamic, and displaced inferolaterally (due to eccentric hypertrophy and increased stroke volume)
Chronic Aortic Regurgitation Findings
Auscultation
- S3 (sign of volume overload)
- High-pitched, blowing, decrescendo early diastolic murmur (as a result of regurgitant, retrograde blood flow over the aortic valve)
AR due to valvular disease → heard best in the left third and fourth intercostal spaces and along the left sternal border (Erb point)
AR due to aortic root disease (e.g., aortic dissection) → heard best along the right sternal border
Worsens with squatting and handgrip (these maneuvers increase afterload)
- Austin Flint murmur
Rumbling, low-pitched, middiastolic or presystolic murmur heard best at the apex
Caused by regurgitant blood striking the anterior leaflet of the mitral valve, which leads to premature closure of the mitral leaflets
- In more severe stages, possibly a harsh, crescendo-decrescendo midsystolic murmur that resembles the ejection murmur heard in aortic stenosis (as a result of a large volume of blood ejected over the aortic valve in an anterograde direction)
- Findings specific to chronic AR → increased LV size and volume due to eccentric hypertrophy and dilation. LV function is often preserved)
ECG shows signs of LVH, ST-segment depression and T-wave inversion in I, aVL, V5, and V6
Chest x-ray shows signs of LVH and enlarged cardiac silhouette
Water Hammer Pulse
Physical exam finding in which palpation of a distal arterial pulse (such as the radial pulse) shows a rapid upstroke followed by prompt collapse of the vessel, (e.g., “bounding pulse”).
Occurs due to rapid and large stroke volume ejection into the arterial system and is most commonly associated with aortic regurgitation.
Referred to as Corrigan’s pulse in the carotid artery and water hammer pulse in the limbs.
Austin Flint Murmur
Rumbling, low-pitched, middiastolic or presystolic murmur heard best at the apex
Caused by regurgitant blood striking the anterior leaflet of the mitral valve, which leads to premature closure of the mitral leaflets
Auscultated in patients with chronic mitral regurgitation
Primary Mitral Regurgitation Etiology
Mitral regurgitation caused by direct involvement of the valve leaflets or chordae tendinae
- Degenerative mitral valve disease (mitral valve prolapse, mitral annular calcification, ruptured chordae tendinae)
- Rheumatic fever
- Infective endocarditis
- Ischemic MR (e.g., papillary muscle rupture following acute MI)
Secondary Mitral Regurgitation Etiology
Caused by changes of the left ventricle that lead to valvular incompetence
- Coronary artery disease or prior myocardial infarction causing papillary muscle involvement
- Dilated cardiomyopathy (e.g., peripartum cardiomyopathy) and left-sided heart failure
Acute Mitral Regurgitation Sign & Symptoms
- Dyspnea
- Symptoms of left-sided heart failure
- Signs and symptoms of pulmonary edema (e.g., bibasilar, fine, late inspiratory crackles)
- Cardiogenic shock → poor peripheral perfusion, tachycardia, tachypnea, and hypotension
- Palpitations (new-onset atrial fibrillation is common in patients with acute MR)
Acute Mitral Regurgitation Findings
Auscultation
- Soft, decrescendo murmur
- No murmur in severe regurgitation with LV systolic dysfunction or hypotension
- Potentially → S3 heart sound
Normal Left atrium
Normal left ventricular size
Normal LV ejection fraction
Elevated pulmonary artery pressure
Normal RV ejection fraction
Troponin elevation may indicate myocardial ischemia.
BNP typically normal because of the acute onset of symptoms
ECG findings are often nonspecific.
Chest x-ray → normal-sized cardiac silhouette
Acute Mitral Regurgitation Management
- All patients with acute primary MR should undergo urgent surgical repair or valve replacement. While awaiting surgery, any symptoms of heart failure should be managed with medical therapy (e.g., diuretics, nitrates, antihypertensive drugs).
- Surgical therapy indications
1. Acute primary MR (urgent surgery)
2. Acute secondary MR that does not adequately respond to medical therapy
Surgical procedures
- Valve repair → preferred option because of the reduced risk of mortality and complications (mitral valve replacement is associated with higher rates of short- and long-term mortality than valve repair. Additionally, most mitral valve replacements are prosthetic rather than biological, because the lifespan of biological valves is short (∼ 10 years); therefore, they risk causing thromboembolism, endocarditis, and hemorrhage as a result of lifelong anticoagulation)
- Valve replacement → may be necessary if there is severe destruction of the mitral valve
- Revascularization therapy → in ischemic MR with papillary muscle rupture
Medical therapy
- For acute primary MR, medical treatment is usually only a temporizing measure while surgery is planned. The aim is to reduce the symptoms of heart failure and improve forward flow.
- Heart failure management (may worsen hypotension; use caution in hemodynamically unstable patients)
1. Vasodilators to reduce afterload and improve cardiac output - Nitroprusside (reduces both pulmonary and systemic vascular resistance, potentially reducing the degree of MR and increasing cardiac output)
- Nitrates (e.g., nitroglycerin) (decreases pulmonary artery pressure and left ventricular preload)
2. Diuretics (e.g., furosemide) for acute pulmonary edema (reduces preload, treats acute pulmonary edema, and may increase cardiac efficiency) - Hypotension → inotropes (e.g., dobutamine )
- Atrial fibrillation → consider cardiac resynchronization therapy to improve hemodynamics.
Chronic Mitral Regurgitation Management
- Management is guided by the symptoms and extent of heart failure and the cause of MR.
- Medical therapy should be initiated in all patients to optimize cardiac function but surgery is the definitive treatment option.
Medical management
- Identify and treat any underlying cause (particularly in secondary MR).
- Heart failure management (ACE inhibitors and beta blockers are thought to favorably affect left ventricular remodeling in MR)
1. Diuretics (e.g., furosemide)
2. ACE inhibitors (e.g., lisinopril)
3. Beta blockers (e.g., metoprolol tartrate)
Surgical management and transcatheter mitral repair
- Chronic primary MR indications
- Asymptomatic patients with LV dysfunction (LVEF 30–60% or LV end-systolic diameter ≥ 40 mm)
- Symptomatic patients with LVEF 30–60 %
- Contraindications → once LVEF is < 30%, surgery is generally not recommended because of the high mortality rate and low likelihood of symptom improvement. (Ventricular remodeling in MR initially appears to be reversible if the valve is repaired; however, by the time severe changes have occurred and LVEF is< 30%, the ventricle does not remodel) - Chronic secondary MR indications
- Consider for patients with severe MR and persistent symptomatic heart failure (NYHA classes III–IV) despite optimal medical management (surgical benefit is less clear because the regurgitation is driven by changes to the ventricle, not the mitral valve, which generally remains normal)
Bundle of His
- Location → directly below the cardiac skeleton, within the membranous part of the interventricular septum
- Receives impulses from the AV node
- Splits into left and right bundle branches (Tawara branches) → the right bundle travels to the right ventricle; the left bundle splits into an anterior and a posterior branch to supply the left ventricle → terminate into terminal conducting fibers (Purkinje fibers) of the left and right ventricle
- Prevents retrograde conduction
- Filters high-frequency action potentials so that high atrial rates (e.g., in atrial fibrillation) are not conducted to the myocardium
- Frequency → ca. 30–40/min
Purkinje Fibers
- Location → terminal conducting fibers in the subendocardium
- Conduct cardiac AP faster than any other cardiac cells
- Ensure synchronized contraction of the ventricles
- Purkinje fibers have a long refractory period.
- Form functional syncytium: forward incoming stimuli very quickly via gap junctions to allow coordinated contraction
- Frequency → ca. 30–40/min
PR-Segment Depression
Atrial injury or inflammation → abnormal atrial repolarization → PR-segment depression
Etiology:
- Pericarditis (note that pericarditis is also associated with ST-segment elevation in multiple leads and can be confused with STEMI. PR-segment depression in the same leads is an indicator of pericarditis)
- Pericardial effusion
- Atrial ischemia or infarction
Pathological Q Waves
Myocardial ischemia → myocyte necrosis beneath the electrode → electrical “window” resulting from dead tissue → electrode reading of electrical activity of opposite myocardial wall → Q wave
ECG findings:
- Abnormally wide (≥ 40 ms)
- Abnormally deep (≥ 0.2 mV or > 25% of the R wave amplitude) or detectable in V1–V3
Etiology:
- Myocardial injury
- Myocardial infarction
- Cardiac infiltrative disease (e.g., sarcoidosis, amyloidosis) - Ventricular enlargement
- Hypertrophic cardiomyopathy
- Hypertensive heart disease
- Other cardiomyopathies - Altered ventricular conduction
- LBBB
- WPW - Acute pulmonary embolism
- Congenital heart disease
- Incorrect placement of the upper limb leads
Dominant R Wave
Increase in the depolarization vector toward lead V1 → tall R wave
ECG findings:
- Tall R wave in lead V1
- Normal in children and young adults
Etiology:
- RVH
- RBBB
- Posterior myocardial infarction
- HCM
- WPW
Poor R-wave Progression
Ventricular depolarization vector reduced or directed posteriorly → deviation of the depolarization vector away from electrodes → insufficient increase in the size of the R wave and deep S waves
ECG findings:
- Absence of the normal increase in the size of R waves from lead V1 to V6
- May be a normal variant
Etiology:
- Anterior wall myocardial infarction
- Right heart strain (e.g., in COPD)
- RVH
- LBBB
- LAFB
- WPW
- Incorrect electrode placement
Persistent S Wave
Ventricular depolarization vector reduced or directed posteriorly → deviation of the depolarization vector away from electrodes → insufficient increase in the size of the R wave and deep S waves
ECG findings:
1. Presence of an S wave in all precordial leads
Etiology:
- Anterior wall myocardial infarction
- Right heart strain (e.g., in COPD)
- RVH
- LBBB
- LAFB
- WPW
- Incorrect electrode placement
Bundle Branch Blocks
Bundle branch blocks → transmission of impulse via remaining functional branch or fascicle → slower ventricular depolarization → long QRS complex
Incomplete bundle branch block: QRS duration of 0.1–0.12 s
Complete bundle branch block: QRS duration ≥ 0.12 s
Left bundle branch block (LBBB)
ECG findings
- No R wave in lead V1
- Deep S waves (forming a characteristic W shape)
- Wide, notched R waves in leads I, aVL, V5, V6 (forming a characteristic M shape)
- Loss of Q waves in the lateral leads
Etiology
- Cardiac
- Coronary artery disease
- Myocardial infarction
- Hypertension
- Myocardial contusion
- Restrictive cardiomyopathy
- Dilated cardiomyopathy - Hyperkalemia
- Digoxin toxicity
- Degenerative disease of the conduction tissue
Right Bundle Branch Block (RBBB)
ECG findings
- An rsr’, rsR’, or rSR’ complex (forming a characteristic “rabbit ears” or M shape) in leads V1, V2
- Tall secondary R wave in lead V1
- Wide, slurred S wave in leads I, V5, V6
- Associated feature: ST segment depression and T-wave inversion in leads V1, V2, and sometimes V3
- Usually a normal axis
- Normal variant in ∼ 5% of individuals
Etiology
- Cardiac
- Coronary artery disease
- Myocardial infarction
- Myocardial contusion
- Mitral stenosis - Pulmonary
- Pulmonary hypertension
- Pulmonary embolism
- COPD - Congenital heart defects
- Atrial septal defect
- VSD
- Pulmonary stenosis
- Tetralogy of Fallot - Brugada syndrome (a pseudo-RBBB)
- Degenerative disease of the conduction tissue
Bifascicular Block
ECG findings
- An RBBB with either of the following:
- Left anterior fascicular block (common form) (in the absence of a concurrent RBBB, the QRS complex would be < 120 ms in addition to the criteria below)
- Left axis deviation
- qR pattern in lead aVL
- Left posterior fascicular block (rare) (in the absence of a concurrent RBBB, the QRS complex would be < 120 ms in addition to the criteria below)
- Right axis deviation
- rS pattern in leads I and aVL
- qR pattern in leads III and aVF
Etiology
- Coronary artery disease
- Valvular heart disease
- Hypertension
- Cardiomyopathies
- Chagas disease
Left Ventricular Hypertrophy (LVH)
Increased muscle mass (hypertrophy) → taller R waves (in leads V5, V6) and S waves (in leads V1, V2)
The amplitude of the QRS complex in the precordial leads is used to assess for ventricular hypertrophy.
ECG findings
- Sokolow-Lyon criteria → RV5 or RV6 + SV1 or SV2 ≥ 3.5 mV
- Left ventricular strain pattern → ST depression with T wave inversion in the left precordial leads in a resting ECG
Etiology:
- Hypertension
- Aortic stenosis
- Coarctation of the aorta
- Mitral regurgitation
- Hypertrophic cardiomyopathy
- Myocarditis
- VSD
Right Ventricular Hypertrophy (RVH)
Increased muscle mass (hypertrophy) → taller R waves (in leads V1, V2) and deeper S waves (in leads V5, V6)
Any of the following may suggest RVH:
- Right axis deviation
- Dominant R wave in lead V1 (R wave > 0.6 mV or R/S > 1)
- Deep S wave in lead V5 (> 1 mV) or V6 (> 0.3 mV)
- Sokolow-Lyon criteria → RV1 or R2 + SV5 or S6 ≥ 1.05 mV
Etiology:
- Pulmonary hypertension
- Pulmonary embolism
- COPD
- Mitral stenosis
- Congenital heart defects
ST Elevation
ECG findings (one of the following):
- ≥ 0.1 mV in limb leads
- ≥ 0.2 mV in precordial leads
Etiology:
- Normal finding → small, concave ST elevations in young, healthy adults due to early repolarization
- STEMI → significant ST elevations in ≥ 2 anatomically contiguous leads (corresponding to occlusion of a specific artery)
- LBBB
- Pericarditis → widespread ST elevations
- Pulmonary embolism
- Perimyocarditis (usually, the ST elevation follows a deepS wave)
- Brugada pattern
- Left ventricular aneurysm
J Wave
Also referred to as Osborn wave
ECG findings:
1. Positive deflection at the J point
Etiology:
- Brugada syndrome
- Idiopathic ventricular fibrillation
- Hypercalcemia
- Hypothermia
Brugada Syndrome
- Rare autosomal dominant genetic mutation that leads to abnormal cardiac conduction and sudden death
- The most common identified mutation affects cardiac voltage-gated sodium channels.
- Most common in Asian men
- Symptoms mostly manifest in adulthood.
Clinical features:
- Often an incidental finding, as most patients are asymptomatic
- Syncope
- Polymorphic ventricular tachycardia
- Ventricular fibrillation
ECG findings
- Brugada pattern: pseudo-RBBB with ST elevation in leads V1–V3
- J waves in leads V1–V3
- Rule out underlying heart disease (e.g., cardiac stress test and echocardiography).
Treatment
- Avoid certain medications (e.g., certain antiarrhythmics, psychotropics, anesthetic agents).
- Avoid excessive alcohol intake, cocaine, and large meals.
- Treat fever with antipyretics.
- Implantable cardiac defibrillator (ICD)
- Screen all first-degree relatives annually with clinical examination and ECG.
Complications
- Sudden cardiac death
- Increased risk of atrial fibrillation
T-wave Inversion
May be due to any of the following:
- Ventricular repolarization vector directed away from the electrode of the ECG lead
- Changes in myocardial cellular electrophysiology (e.g., during ischemia or infarction)
- Changes in the sequence of ventricular activation (e.g., in bundle branch blocks or cardiac hypertrophy)
ECF findings
- Amplitude ≥ -0.1 mV
- May be a normal finding in:
- Leads III, aVR, or V1 (May also be normal in lead V2 if T-wave inversion in lead V1 is also present)
- Children - New-onset T-wave inversion (i.e., not present on the patient’s previous ECGs)
Etiology:
- Coronary artery disease (myocardial ischemia)
- Bundle branch blocks
- Pulmonary embolism (pulmonary embolism is known to produce an S1Q3T3 pattern: a deep S wave in lead I, Q wave in lead III, and inverted T wave in lead III)
- Perimyocarditis (pericarditis initially causes diffuse, saddle-shaped ST elevation followed by T-wave inversion)
- Ventricular hypertrophy
- Digoxin
- Intracranial hemorrhage (asymmetric T wave inversion)
- Persistent juvenile T-wave pattern
- Wellens syndrome (symmetrical T wave inversion)
T-wave Flattening
May be due to any of the following:
- Ventricular repolarization vector directed away from the electrode of the ECG lead
- Changes in myocardial cellular electrophysiology (e.g., during ischemia or infarction)
- Changes in the sequence of ventricular activation (e.g., in bundle branch blocks or cardiac hypertrophy)
ECG findings:
- Amplitude between 0.1 mV and -0.1 mV
- T wave appears flatter than normal.
Etiology:
- Hypokalemia
- Hypoglycemia
- Myocardial ischemia
- Hypothyroidism
Peaked T Wave
May be due to any of the following:
- Ventricular repolarization vector directed away from the electrode of the ECG lead
- Changes in myocardial cellular electrophysiology (e.g., during ischemia or infarction)
- Changes in the sequence of ventricular activation (e.g., in bundle branch blocks or cardiac hypertrophy)
ECG findings:
1. Tall, narrow, symmetrically peaked
Etiology:
- Hyperkalemia
- Hypermagnesemia
- High vagal tone
Hyperacute T Wave
May be due to any of the following:
- Ventricular repolarization vector directed away from the electrode of the ECG lead
- Changes in myocardial cellular electrophysiology (e.g., during ischemia or infarction)
- Changes in the sequence of ventricular activation (e.g., in bundle branch blocks or cardiac hypertrophy)
ECG findings:
1. Broad, asymmetrically peaked
Etiology:
- Early stages of a STEMI (often precedes ST elevation and Q waves)
- Prinzmetal angina (induces ischemia and leads to hyperacute T waves as in STEMI)
Biphasic T Wave
May be due to any of the following:
- Ventricular repolarization vector directed away from the electrode of the ECG lead
- Changes in myocardial cellular electrophysiology (e.g., during ischemia or infarction)
- Changes in the sequence of ventricular activation (e.g., in bundle branch blocks or cardiac hypertrophy)
ECG findings:
- T wave consisting of an upward and downward deflection
- The initial deflection is variable and can be either up or down.
Etiology:
- Initial positive deflection
- Acute myocardial ischemia
- Wellens syndrome - Initial negative deflection: hypokalemia
Shortened QT Interval
Abnormal ventricular depolarization or repolarization (depending on the etiology) → shortened QT interval
ECG findings:
1. < 390 ms (some sources describe different cutoff values for a shortened QT interval.)
Etiology:
- Hypercalcemia
- Hyperkalemia
- Digoxin effect
- Increased sympathetic tone (e.g., hyperthyroidism, fever)
- Congenital short QT syndrome
U Wave
- Small deflection after the T wave
- Polarity is the same as the T wave
- Best seen in leads V2 to V4, but not always visible
- Normal finding in athletes
Etiology
- Exact origin is unknown
- Thought to be due to delayed repolarization of the midmyocardial cells (myocardium) and the His-Purkinje system
Causes of prominent U waves
- Hypokalemia
- Hypercalcemia
- Bradycardia
Acquired Long QT Syndrome
Drug-induced LQTS (usually substances that block potassium outflow during the rapid repolarization phase)
- Antiarrhythmics
- Class Ia (e.g., quinidine, disopyramide, procainamide)
- Class III (e.g., sotalol; uncommonly, amiodarone) - Antibiotics (e.g., macrolides, fluoroquinolones)
- Antihistamines (e.g., diphenhydramine)
- Antidepressants (most tricyclic antidepressants and tetracyclic antidepressants, some SSRIs, lithium)
- Antipsychotics (e.g., haloperidol, ziprasidone)
- Anticonvulsants (e.g., fosphenytoin, felbamate)
- Antiemetics (ondansetron)
- Antifungals (e.g., azoles)
- Antiparkinson medications
- Opioids
Electrolyte imbalances → hypokalemia, hypomagnesemia, hypocalcemia
Acute CNS insult→ ischemic stroke or intracranial hemorrhage (QT prolongation is one of the most frequent ECG abnormalities seen following ischemic stroke or intracranial hemorrhage)
Endocrine disorders → hypothyroidism
Nutritional deficiencies → severe vitamin D deficiency (uncommon) (anorexia nervosa was previously thought to be associated with acquired LQTS. However, a long-term follow-up study published by the American heart association (AHA) found no evidence to support this)
Wolff-Parkinson-White Syndrome (WPW)
- Congenital condition characterized by intermittent tachycardias and signs of ventricular preexcitation on ECG, both of which arise from an accessory pathway known as the bundle of Kent
- A congenital accessory pathway, the bundle of Kent, connects the atria and ventricles, bypassing the AV node and leading to ventricular preexcitation.
- May be associated with structural abnormalities of the heart, in particular Ebstein anomaly
- ∼ 10% of patients have multiple accessory pathways (more common with coexisting structural heart disease).
- The prevalence of WPW pattern is 0.1–0.2% in the general population and 0.55% in first-degree relatives.
- A proportion of these cases is due to familial WPW syndrome, a rare autosomal-dominant genetic disorder that causes conduction abnormalities and hypertrophic cardiomyopathy.
- ♂ > ♀
- Symptoms typically develop at 20–40 years of age.
- May be asymptomatic (WPW pattern) or associated with arrhythmias (WPW syndrome), including:
1. AVRT (most common; 80%)
2. Atrial fibrillation (15–35%; incidence increases with age)
3. Atrial flutter (5%)
4. Others (rare): MAT, FAT, ventricular fibrillation
ECG findings in WPW:
While in sinus rhythm, a preexcitation pattern may be present.
- Short PR interval (this is shortened due to the earlier activation of the ventricle through the accessory pathway)
- ECG delta wave → a slurred upstroke at the start of the QRS complex, secondary to preexcitation (this reflects partial early-onset slow ventricular depolarization through the bypass tract, which is then interrupted by the rapid depolarization of the rest of the ventricle through the His-Purkinje system. ECG delta wave is not seen in all patients)
- Widened QRS (due to the abnormal depolarization of the ventricle, which occurs slowly, myocyte to myocyte, rather than through the rapidly conducting Purkinje fibers)
Can show any of the arrhythmias associated with WPW
WPW with atrial fibrillation or flutter
- Heart rate may be very high (> 200–250/minute) because impulses from the atria are transmitted via the accessory pathway directly to the ventricles, bypassing the AV node. (The refractory period of the accessory pathway may be extremely short, allowing very rapid transmission)
- Wide QRS complexes are commonly seen because of ventricular preexcitation.
- Appearance may be very similar to that of polymorphic ventricular tachycardia
Paroxysmal Supraventricular Tachycardia (PSVT)
- Any SVT with a narrow QRS complex and an abrupt onset
- Most commonly caused by AV nodal reentry
- Commonly presents with sudden-onset palpitations, diaphoresis, lightheadedness.
- Treatment → terminate re-entry by slowing AV node conduction (eg, vagal maneuvers, IV adenosine). Electrical cardioversion if hemodynamically unstable. Definitive treatment is catheter ablation of re-entry tract.
Atrial Fibrillation Risk Factors
Cardiovascular risk factors
- Advanced age
- Hypertension
- Diabetes mellitus
- Smoking
- Obesity
- Sleep apnea
Intrinsic cardiac disorders
- Coronary artery disease
- Valvular heart disease (especially mitral valve disease) (atrial fibrillation is much more common in patients with mitral stenosis than in those with mitral regurgitation. Approximately two-thirds of patients with mitral stenosis will develop atrial fibrillation at some point)
- Congestive heart failure (CHF)
- Preexcitation tachycardia. e.g., Wolff-Parkinson-White (WPW) syndrome (atrial fibrillation occurs in approx. 20% of patients with WPW syndrome)
- Sick sinus syndrome (tachycardia-bradycardia syndrome)
- Cardiomyopathies
- Pericarditis
- Congenital channelopathies
Noncardiac disorders
- Pulmonary disease → COPD, pulmonary embolism, pneumonia
- Hyperthyroidism (increases the response of the heart to sympathetic stimulation)
- Catecholamine release and/or increased sympathetic activity
- Stress → sepsis, hypovolemia, post-surgical state (especially following cardiac surgery), hypothermia
- Pheochromocytoma
- Cocaine, amphetamines
- Electrolyte imbalances (hypomagnesemia, hypokalemia)
- Drugs → e.g., adenosine, digoxin
- Holiday heart syndrome → irregular heartbeat classically triggered by excessive alcohol consumption, but also sometimes by moderate alcohol consumption, stress, dehydration, or lack of sleep
- Chronic kidney disease (reduced renal function can lead to hypertension, LVH, and, eventually, atrial stretch and fibrosis, which are predictors of Afib. CKD can also activate the renin-angiotensin-aldosterone system, which can result in atrial remodeling and fibrosis.)
Complications of Long-Standing Atrial Fibrillation
- Acute left heart failure → pulmonary edema
- Thromboembolic events → stroke/TIA, renal infarct, splenic infarct , intestinal ischemia , acute limb ischemia
- Life-threatening ventricular tachycardia
Atrial Flutter
- Supraventricular tachyarrhythmia that is usually caused by a macroreentrant rhythm within the atria.
- ♂ > ♀ (incidence in men is 2.5 times greater than in women)
- Etiology → similar to atrial fibrillation. May additionally result from the treatment of Afib (treatment with flecainide, propafenone, or amiodarone is associated with developing atrial flutter)
- Unlike that of Afib, the reentrant rhythm in atrial flutter is well-defined.
- Type I (common; typical or isthmus-dependent flutter) → caused by a counterclockwise (more common) or clockwise (less common) macroreentrant activation of cardiac muscle fibers in the right atrium that travels along the tricuspid annulus and passes through the cavotricuspid isthmus
- Type II (rare; atypical atrial flutter) → various reentrant rhythms that do not involve the cavotricuspid isthmus, are not well-defined, and/or occur in the left atrium
- Most patients are asymptomatic. Less commonly → symptoms of arrhythmias, such as palpitations, dizziness, syncope, fatigue, and or dyspnea
- Tachycardia with a regular pulse
- Symptoms of the underlying disease (e.g., murmurs of mitral stenosis) may be present.
- Diagnostics:
1. Similar to atrial fibrillation except for ECG findings
2. Rate → typically 75–150/minute (depending on conduction)
3. Atrial rate ≥ ventricular rate
4. Regular, narrow QRS complexes (when there is no aberrant conduction)
5. The rhythm may be: - Regularly irregular if atrial flutter occurs with a variable AV block occurring in a fixed pattern (2:1 or 4:1)
- Irregularly irregular with a variable block occurring in a nonfixed pattern
6. Sawtooth appearance of P waves → identical flutter waves (F waves) that occur in sequence at a rate of ∼ 300/minute
Treatment:
- Same as Afib
- Rate control → more difficult to achieve in atrial flutter than in Afib
- Rhythm control
- Better results and lower recurrence compared to Afib
- Catheter ablation may be the most effective rhythm control strategy. - The same parameters for anticoagulation in Afib are recommended
Complications
- Frequently degenerates into atrial fibrillation
- 1:1 conduction leading to life-threatening ventricular tachycardia
Ventricular Fibrillation Etiology
- Underlying cardiovascular disease
- Most common → coronary artery disease (CAD)
- Others → previous myocardial infarction, myocarditis, cardiomyopathy, severe congestive heart failure, heart valve disease - Congenital heart defects (e.g., pulmonary atresia) (the term congenital heart defects only refers to structural abnormalities.)
- Electrolyte imbalances (e.g., hypokalemia, hyperkalemia)
- Electrophysiologic disorders
- Wolff-Parkinson-White syndrome
- Long-QT syndrome → torsade de pointes (long-QT syndrome can lead to V-fib directly, or may evolve to torsade de pointes tachycardia, which commonly leads to V-fib, syncope, and/or sudden cardiac death.)
Etiology of Atrioventricular Blocks
Structural heart disease
- Ischemic heart disease
- Acute MI (AV block is common in the period immediately following an MI. Blocks resulting from anterior MI are more likely to be of a higher degree or progress to complete AV block and less likely to be reversible than blocks following inferior MI)
- Chronic ischemic cardiomyopathy (both chronic ischemic cardiomyopathy and angina (either unstable or variant) can cause AV blocks) - Congenital heart disease and congenital third-degree AV block
- Post-cardiac intervention → e.g., surgery (particularly involving valves), ablations, or TAVI
- Inflammatory/infiltrative cardiomyopathy → e.g., myocarditis, amyloidosis, sarcoidosis, autoimmune connective tissue disorders, lymphoma (primary cardiac lymphomas can infiltrate the AV node, causing AV block.)
- Degenerative → idiopathic fibrosis of the conduction system (Lenègre-Lev syndrome) causing RBBB and eventually AV block
Neurocardiogenic
- Increased vagal tone (can be physiological or pathological)
- Healthy individuals with high levels of exercise (e.g., in professional athletes) → most often transient 1° AV block and Mobitz I
- Obstructive sleep apnea
- During vomiting, suctioning, or intubation
Toxic/metabolic
- Electrolyte disorders → e.g., hyperkalemia
- Acid-base disorders
- Cardiotoxic drugs → e.g., beta blockers, calcium channel blockers, or digoxin (therapeutic doses or overdoses)
- Other toxicity → e.g., carbon monoxide, cyanide
Infectious
- Bacterial endocarditis
- Lyme carditis
- Acute rheumatic fever
Endocrine
- Thyroid disease
- Adrenal disease
Neuromuscular
1. Myotonic dystrophy
Stokes-Adams Attacks
- Sudden losses of consciousness that may occur with brief prodromal symptoms, e.g., dizziness, or without any warning, usually lasting a few seconds
- Attacks are caused by ventricular asystole, most commonly due to third-degree heart block, especially idiopathic paroxysmal AV block. Other possible causes include second-degree Mobitz type II AV block or ventricular arrhythmias.
Atrial Reflex
- Physiologic reflex characterized by an increased heart rate in response to atrial distention (increased venous return to the heart).
- Mediated by stretch receptors in the atria.
- Mechanisms of action: ↑ Volume → ↑ atrial stretch receptors stimulation → activation of stretch receptors (B-fibers) in the atria → ↑ sympathetic innervation and no change in parasympathetic innervation → ↑ HR
Diuresis Reflex (Gauer-Henry Reflex)
Physiological reflex that adapts ADH release in the hypothalamus according to blood pressure
Mechanisms of action
- ↑ BP: Atrial stretch receptors inhibit ADH release via afferent vagal fibers → ↑ water excretion by the kidneys
- ↓ BP: ↑ ADH release → ↓ water excretion by the kidneys
Cushing reflex
Triad of hypertension, bradycardia, and respiratory depression
↑ intracranial pressure → compensatory constriction of cerebral arterioles → ↓ cerebral perfusion → hypercapnia and acidosis → chemoreceptor mediated sympathetic response → ↑ blood pressure → stimulation of aortic arch baroreceptors → activation of the parasympathetic nervous system (vagus) → reflex bradycardia
Vascular Compliance
Ability of a vessel to expand in response to changes in pressure
C = ΔV/ΔP
- C = compliance (mL/mm Hg)
- ΔV = change in volume (mL)
- ΔP = change in pressure (mm Hg)
Greater compliance → greater increase in vascular volume during an increase in pressure (e.g., elastic arteries)
Less compliance → less increase in vascular volume during an increase in pressure (e.g., muscular arteries)
Compliance is mainly determined by the muscle tone of vessel walls. Arterioles, which are abundant in smooth muscle, have low compliance and are, therefore, considered resistance vessels. Veins are less abundant in smooth muscle, have much higher compliance, and are considered capacitance vessels.
Vascular Elastance
Ability of a vessel to adapt to intraluminal pressure in response to changes in volume (i.e., the reciprocal of compliance)
E’ = ΔP/ΔV
- E’ = elastance (mm Hg/mL)
- C = compliance (mL/mm Hg)
- ΔP = change in pressure (mm Hg)
- ΔV = change in volume (mL)
Greater elastance → greater change in blood pressure during blood volume change
Less elastance → less change in blood pressure during blood volume change
Myogenic Autoregulation
Myocytes in the walls of arteries and arterioles react to changes in blood pressure to maintain constant blood flow in the blood vessels.
Mechanism of action: ↑ BP → ↑ transmural pressure in arteries and arterioles (e.g., during strenuous exercise, the transition from supine to upright position) → stretch-activated ion channels opening up in myocytes → myocyte depolarization and subsequent Ca2+ influx → smooth muscle contraction → vasoconstriction
Sites of action→ almost all organs (especially the kidneys and brain) except the lungs
Particularly important in the kidneys because it maintains constant renal blood flow and, in turn, constant GFR when systemic blood pressure fluctuates.
Tubuloglomerular Feedback
Mechanism by which macula densa cells regulate glomerular filtration rate (GFR).
In response to high sodium chloride concentration (which indicates high GFR), the macula densa releases ATP and adenosine, which act on the myogenic juxtaglomerular cells of the afferent arteriole to cause vasoconstriction and reduce GFR.
In response to low sodium chloride concentration (which indicates low GFR), the macula densa releases PGE2, which acts on the juxtaglomerular cells and causes renin release to increase GFR.
Primary (essential) hypertension Nonmodifiable Risk Factors
Positive family history
Ethnicity
Advanced age
Primary (essential) Hypertension Modifiable Risk Factors
Obesity Diabetes Smoking, excessive alcohol or caffeine intake Diet high in sodium, low in potassium Physical inactivity Psychological stress
Secondary Hypertension Etiology
Caused by an identifiable underlying condition
Renal hypertension
- Renovascular hypertension (the most common cause of secondary hypertension) can be due to:
- Renal artery stenosis
- Polyarteritis nodosa
- Fibromuscular dysplasia of the renal arteries - Polycystic kidney disease (ADPKD)
- Renal failure (renal parenchymal hypertension) (includes all renal diseases that involve advanced impairment of the glomerular filtration rate (GFR))
- Glomerulonephritis
- Systemic lupus erythematosus
- Renal tumors
- Atrophic kidney
Endocrine hypertension
- Primary hyperaldosteronism
- Hypercortisolism (Cushing syndrome)
- Hyperthyroidism
- Pheochromocytoma
- Primary hyperparathyroidism
- Acromegaly
- Congenital adrenal hyperplasia (17α-hydroxylase and 11β-hydroxylase deficiency cause hypertension)
Other
- Coarctation of the aorta
- Obstructive sleep apnea
Medication → sympathomimetic drugs, corticosteroids, NSAIDs, oral contraceptives (hypertension is common in women > 35 years of age who are obese and have been taking birth control pills for an extended period of time)
Recreational drug use → amphetamines, cocaine, phencyclidine
Isolated systolic hypertension
Isolated systolic hypertension (ISH)
Increase in systolic blood pressure (≥ 140 mm Hg) with diastolic BP within normal limits (≤ 90 mm Hg)
Etiology
- ISH in elderly → decreased arterial elasticity and increased stiffness → decreased arterial compliance
- ISH secondary to increased cardiac output
- Anemia
- Hyperthyroidism
- Chronic aortic regurgitation
- AV fistula
Clinical features:
- Often asymptomatic
- Signs of increased pulse pressure → e.g., head pounding, rhythmic nodding, bobbing of the head in synchrony with heartbeats
Treatment → thiazide diuretics OR dihydropyridine calcium antagonists
Prognosis → high risk of cardiovascular events (MI, stroke, renal dysfunction)
Difference in Blood Pressure in Both Arms
Takayasu arteritis
Aortic dissection
Aortic arch syndrome
Subclavian steal syndrome
Difference in Blood Pressure of Upper and Lower Limbs
Coarctation of the aorta distal to the left subclavian artery
Eruptive Xanthoma Associated Conditions
Hypertriglyceridemia (chylomicron or VLDL)
Lipoprotein lipase deficiency (familial hyperchylomicronemia)
Yellow papules with an erythematous border
May be tender and itchy
Location → buttocks, back, and extensor surfaces of the extremities
Tuberous Xanthoma Associated Conditions
Severe hypercholesterinemia (↑ LDL and/or VLDL levels)
Firm, painless, reddish-yellow nodules located in pressure areas
Location → knees, elbows, heels, and buttocks
Tendinous Xanthoma Associated Conditions
Severe hypercholesterinemia (↑ LDL and/or VLDL levels)
Firm nodules, located in tendons
Location → extensor tendons of hands and Achilles tendon
Palmar Xanthoma Associated Conditions
Type III hyperlipoproteinemia (↑ VLDL levels)
Biliary cirrhosis
Yellow plaques
Location → Palms of the hands
Plane Xanthoma Associated Conditions
Lymphoma
Leukemia
Plasmacytomas
Yellow, thin plaques
Location → Larger body areas, e.g., trunk, neck, shoulders
Lipemia Retinalis
Opaque, white appearance of the retinal vessels, visible on fundoscopic exam
Associated with hyperlipoproteinemia type I, III, and IV
Arcus Lipoides Corneae
Associated with hyperlipoproteinemia type II
Not pathological in advanced age
Atherosclerosis Modifiable Risk Factors
- Smoking (daily consumption of 10 cigarettes increases cardiovascular mortality by approx. 20% in males and 30% in females)
- Diabetes mellitus (main cause of death in diabetic patients (accounting for 80% of deaths))
- Arterial hypertension (pertains to diastolic and systolic values. The mortality rate of CAD increases in proportion to arterial blood pressure.)
- Dyslipidemia
- High homocysteine levels (homocystinuria)
- Obesity (truncal obesity, in particular, is a risk factor.)
- High fibrinogen levels
- Hyperphosphatemia
- Stress
- Increased alcohol consumption
Atherosclerosis Nonmodifiable Risk Factors
- Family history → cardiovascular events in first-degree relatives below the age of 55 (♂) 65 (♀)
- Age → males ≥ 45 years, females ≥ 55 years (postmenopause)
Pathogenesis Atherosclerosis
- Chronic stress on the endothelium (e.g., due to arterial hypertension and turbulence)
- Endothelial dysfunction, which leads to
- Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
- Adhesion of platelets to the damaged vessel wall → platelets release inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
- PDGF stimulates migration and proliferation of smooth muscle cells (SMC) in the tunica intima and mediates differentiation of fibroblasts into myofibroblasts - Inflammation of the vessel wall
- Macrophages and SMCs ingest cholesterol from oxidized LDL (LDL enters through the damaged vessel wall, accumulates, and is oxidized by free radicals) and transform into foam cells.
- Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
- Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque (atheroma) (macrophages, smooth muscle cells, lymphocytes and extracellular matrix form a fibrous cap, which covers a necrotic center, consisting of foam cells, free cholesterol crystals, and cellular debris.)
- Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
- Calcification of the intima (the amount and pattern of calcification affect the risk of complications) (large, diffuse calcifications stabilize the plaque, while small, scattered calcifications are associated with a higher risk of plaque rupture.)
- Plaque rupture (unstable plaques pose the highest risk. Rupture occurs even at sites of moderate stenosis (< 50%)) → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material
Abdominal Aortic Aneurysm Risk Factors
- Advanced age
- Smoking (most important risk factor)
- Nicotine and other components of smoke cause cell damage, inflammation and impaired cell repair in vascular smooth muscle cells. This weakens the vessel wall resulting in an increased risk of developing an aneurysm and aneurysmal rupture. Patients should therefore be encouraged to stop smoking. - Atherosclerosis
- Hypercholesterolemia and arterial hypertension
- Positive family history
- Trauma
Abdominal Aortic Aneurysm Approach
- Unstable patients (e.g., in case of rupture) → emergency repair within 90 minutes
- Symptomatic patients with impending rupture or leaking AAA → urgent aneurysm repair within hours
- Asymptomatic patients → elective aneurysm repair or aneurysm surveillance
- All patients → reduction of cardiovascular risk factors. Appropriate medical management of other atherosclerotic risk factors (e.g., hypertension, diabetes, hyperlipidemia) and smoking cessation (reduces risk of expansion and rupture)
Abdominal Aortic Aneurysm Invasive Treatment Indications
Emergency repair → unstable patients
Urgent repair → impending rupture or leaking AAA
Elective repair
- Fusiform aneurysm with maximum diameter ≥ 5.5 cm and low or acceptable surgical risk
- Small fusiform aneurysm expanding ≥ 1 cm per year
- Saccular aneurysm (because saccular aneurysms are rare, there is insufficient data to guide recommendations for a repair threshold. Repair is usually indicated at a smaller diameter than in fusiform aneurysms because saccular aneurysms have a higher risk of rupture)
- Aneurysm with maximum diameter 5.0–5.4 cm in women (at this diameter, the risk for rupture is greater for women than men)
- Small aneurysm (4.0–5.4 cm) in patients requiring chemotherapy, radiotherapy, solid organ transplantation → individual approach
Abdominal Aortic Aneurysm Rupture Risk Factors
- Rapidly expanding aneurysm
- Large diameter aneurysm
- Smoking, tobacco use
Thoracic Aortic Aneurysm Risk Factors
- Smoking
- Advanced age
- Arterial hypertension
- Trauma
- Tertiary syphilis (due to obliterative endarteritis of the vasa vasorum)
- Connective tissue diseases (e.g., Marfan syndrome, Ehlers-Danlos syndrome)
- Bicuspid aortic valve
- Positive family history
- Rare → vasculitis/infectious diseases with aortic involvement (e.g., Takayasu arteritis) (mainly associated with TAAs of the ascending aorta, but are a rare cause of AAAs as well)
Aortic Dissection Etiology
Acquired
- Hypertension (most common risk factor)
- Approx. 70% of patients with aortic dissection have elevated blood pressure, which can lead to propagation of the dissection and increases the risk of rupture.
- Exception → in patients < 40 years of age, less than 40% of cases are due to hypertension. - Trauma (e.g., deceleration injury in a motor vehicle accident, or iatrogenic injury during valve replacements or graft surgery)
- Vasculitis with aortic involvement (e.g., syphilis, Takayasu arteritis)
- Use of amphetamines and cocaine
- Third-trimester pregnancy (or early postpartum period)
- Atherosclerosis
Congenital
- Connective tissue disease (Marfan syndrome, Ehlers-Danlos syndrome)
- Bicuspid aortic valve
- Coarctation of the aorta
Stanford Classification for Aortic Dissection
Stanford classification groups dissections by whether the ascending or descending aorta is involved.
- Stanford type A aortic dissection
- Any dissection involving the ascending aorta (defined as proximal to the brachiocephalic artery), regardless of origin
- Can extend proximally to the aortic arch and distally to the descending aorta
- Generally requires surgery
- Complications include aortic regurgitation and cardiac tamponade. - Stanford type B aortic dissection
- Any dissection not involving the ascending aorta
- Descending aorta; originating distal to the left subclavian artery
- Most cases can be managed with medical therapy (e.g., beta blockers, vasodilators).
DeBakey Classification for Aortic Dissection
DeBakey classification categorizes dissections according to their origin and extent.
- Type I
- Dissections originate in the ascending aorta and continue to at least the aortic arch but typically as far as the descending aorta.
- Generally requires surgery - Type II
- Dissections originate in, and are restricted to, the ascending aorta.
- Generally requires surgery - Type III
- Dissections originate in the descending aorta and most often extend distally.
- Most cases can be managed by medical therapy.
- Can be further subdivided into: - Type IIIa → limited to the descending thoracic aorta above the level of the diaphragm
- Type IIIb → extends below the diaphragm
Complications of Stanford type A Dissections
- Myocardial infarction (coronary artery occlusion)
- Aortic regurgitation (extension of the dissection into the aortic valve): new diastolic heart murmur and (exertional) dyspnea
- Cardiac tamponade combined with cardiogenic shock
- Pericarditis (slow extension of the dissection into the pericardium)
- Stroke (extension of the dissection into the carotids)
Complications of both Stanford type A dissection and Stanford type B dissections (as Stanford type A dissections can also extend to the abdominal aorta, both dissection types have several complications in common)
- Bleeding into the thorax, mediastinum, and abdomen
- Arterial occlusion followed by ischemia of the:
- Celiac trunk, superior/inferior mesenteric artery → acute abdomen, ischemic colitis
- Renal arteries → acute renal failure (oliguria, anuria)
- Spinal arteries → weakness of lower extremities or acute paraplegia
- Complete occlusion of the distal aorta → Leriche syndrome (aortoiliac occlusive disease)
Complications of Both Stanford Type A Dissection and Stanford Type B Dissection
- Bleeding into the thorax, mediastinum, and abdomen
- Arterial occlusion followed by ischemia of the:
- Celiac trunk, superior/inferior mesenteric artery → acute abdomen, ischemic colitis
- Renal arteries → acute renal failure (oliguria, anuria)
- Spinal arteries → weakness of lower extremities or acute paraplegia
- Complete occlusion of the distal aorta → Leriche syndrome (aortoiliac occlusive disease)
As Stanford type A dissections can also extend to the abdominal aorta, both dissection types have several complications in common
Deadly Causes of Acute Chest Pain
- Aortic dissection
- Pneumothorax
- Myocardial infarction
- Unstable angina
- Pulmonary embolism
Coronary Flow Reserve (CFR)
The difference between maximum coronary blood flow and coronary flow at rest (a measure of the ability of the coronary capillaries to dilate and increase blood flow to the myocardium).
In healthy individuals, the CFR can be up to 4 times higher on exertion than at rest.
CFR is reduced in individuals with CAD due to vascular stenosis and reduced vascular compliance.
Myocardial Stunning
Acutely ischemic myocardial segments with transiently impaired but completely reversible contractility
Hibernating Myocardium
Both myocardial metabolism and function are reduced to match a concomitant reduction in coronary blood flow (due to moderate/severe flow-limiting stenosis).This new equilibrium prevents myocardial necrosis.
Chronically hibernating myocardium demonstrates decreased expression and disorganization of contractile and cytoskeletal proteins, altered adrenergic control, and reduced calcium responsiveness. These changes lead to decreased contractility and left ventricular (LV) systolic dysfunction.
Coronary revascularization (e.g., after angioplasty or coronary artery bypass grafting) and subsequent restoration of blood flow to hibernating myocardium improves contractility and LV function (partially or completely reversible).
Seen in angina pectoris, left ventricular dysfunction, and/or heart failure
Myocardial Oxygen Supply-Demand Mismatch
Factors reducing oxygen supply
- Coronary atherosclerosis (reduces coronary compliance and narrows the arterial lumen, which reduces blood supply at rest) and sequelae, including:
- Rupture of an unstable atherosclerotic plaque (most common cause)
- Thrombosis
- Stenosis - Vasospasms
- ↑ Heart rate (perfusion of the coronary arteries occurs during diastole. A higher heart rate shortens diastole, thereby reducing perfusion)
- Anemia (is a condition that not only decreases oxygen supply, but also increases oxygen demand, as it can indirectly increase the heart rate)
Factors increasing oxygen demand (e.g., during physical activity or in chronic hypertension)
- ↑ Heart rate
- ↑ Afterload
- Anemia
An increased heart rate reduces oxygen supply and increases oxygen demand.
Subclavian Steal Syndrome
Etiology
- Atherosclerosis
- Takayasu’s arteritis
- Thoracic surgery
Stenosis of the subclavian artery proximal to the origin of the vertebral artery (left subclavian artery ∼ 70% of cases) → hypoperfusion distal to the stenosis → reversal of blood flow in ipsilateral vertebral artery → compensation through collateral arteries (contralateral subclavian artery → contralateral vertebral artery → ipsilateral vertebral artery → ipsilateral subclavian artery) → reduced blood flow in the basilar artery → reduced cerebral perfusion upon exertion involving the affected arm
Clinical Features
- Most patients are asymptomatic
- Limb ischemia (on exertion)
1. Pain, paresthesia
2. Pale, cool skin
3. Weak, delayed radial pulse
4. Disparity in BP > 15 mm Hg - Neurologic symptoms (due to vertebrobasilar insufficiency)
1. Dizziness, vertigo
2. Ocular findings (e.g., diplopia)
3. Syncope
Coronary-subclavian steal syndrome subtype → in patients with an internal thoracic artery (internal mammary artery) bypass. Stenosis of the subclavian artery proximal to origin of the internal mammary artery (IMA) → exertion of the ipsilateral arm → flow reversal in the IMA graft → symptoms of angina pectoris
Imaging of the cerebral and upper extremity arteries, e.g., via Doppler ultrasound, duplex ultrasound, or magnetic resonance angiography, shows reversal of blood flow and/or atherosclerosis.
Treatment:
- Asymptomatic patients usually do not require treatment apart from lifestyle changes to prevent progression of atherosclerosis.
- Symptomatic patients → angioplasty and stenting or surgical revascularization
Vasospastic Angina (previously called Variant or Prinzmetal Angina)
- Caused by transient coronary spasms (usually due to spasms occurring close to areas of coronary stenosis)
- Not affected by exertion (may also occur at rest)
- Typically occurs early in the morning
- Highest prevalence in Japanese population (especially young women)
- Average age of onset → 50 years
Etiology
- Cigarette smoking
- Use of stimulants (e.g., cocaine, amphetamines), alcohol, or triptans
- Stress, hyperventilation, exposure to cold
- Associated with other vasospastic disorders (e.g., Raynaud phenomenon, migraine headaches)
- Common atherosclerotic risk factors (except smoking) do not apply to vasospastic angina.
Diagnostics
- Reversible ST elevation on ECG
- No troponin I or troponin T elevations on serial measurements
- Coronary spasms on angiography confirm the diagnosis.
Treatment
- Lifestyle modification (especially smoking cessation)
- Calcium channel blockers (CCBs) → first-line agents for acute attacks and prophylaxis
- Long-acting nitrates
- Avoid beta-blockers (blockage of the β2-receptors prevents smooth muscle cells from relaxation, thus causing additional vasoconstriction and ischemia in patients with preexisting vasospastic angina. This effect is dose-dependent and may also occur with selective beta blockers)
Prognosis
- The 5-year survival rate is > 90% (with treatment).
- Persistence of symptoms is common.
Acute coronary syndrome
A set of three clinical entities with similar pathophysiology → unstable angina pectoris, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
Most commonly caused by atherosclerotic coronary artery disease associated with unstable plaques and -in the case of myocardial infarction- plaque rupture.
Clinical Triad in Right Ventricular Infarction
Hypotension
Elevated jugular venous pressure
Clear lung fields
Microscopic Changes After 0-4 Hours of Myocardial Infarction
No visible change
Microscopic Changes After 4-12 Hours of Myocardial Infarction
Wavy fibers with narrow, elongated myocytes
Microscopic Changes After 12-24 Hours of Myocardial Infarction
Myocyte hypereosinophilia with pyknotic (shrunken) nuclei
Microscopic Changes After 1-3 Days of Myocardial Infarction
Coagulation necrosis (loss of nuclei & striations) Prominent neutrophilic infiltrate
Microscopic Changes After 3-7 Days of Myocardial Infarction
Disintegration of dead neutrophils & myofibers
Macrophage infiltration at border areas
Microscopic Changes After 7-10 Days of Myocardial Infarction
Robust phagocytosis of dead cells by macrophages
Beginning formation of granulation tissue at margins
Microscopic Changes After 10-14 Days of Myocardial Infarction
Well developed granulation tissue with neovascularization
Microscopic Changes After 2 Weeks - 2 Months of Myocardial Infarction
Progressive collagen deposition & scar formation
Complications After 24 Hours of Myocardial Infarction
Sudden cardiac death
Arrhythmias (a common cause of death in MI patients in the first 24 hours)
Acute left heart failure (death of affected myocardium → absence of myocardial contraction → pulmonary edema)
Cardiogenic shock
Complications After 1-3 Days of Myocardial Infarction
Early infarct-associated pericarditis (postinfarction fibrinous pericarditis)
Complications After 3-14 Days of Myocardial Infarction
Papillary muscle rupture → mitral regurgitation
Ventricular septal rupture → left-to-right shunt
Left ventricular free wall rupture → tamponade
Left ventricular pseudoaneurysm (risk of rupture)
Complications After 2 Weeks to Months of Myocardial Infarction
Atrial ventricular aneurysms
Dressler syndrome
Arrhythmias
Congestive heart failure
Reinfarction
Dilated Cardiomyopathy Etiology
- Mostly idiopathic
- Gene mutations with familial incidence including:
- Mutations of TTN gene, encoding for the intrasarcomeric protein titin (connectin)
- Mutations of MYH7 gene, encoding for the β-myosin heavy chain
- Hemochromatosis
- Duchenne muscular dystrophy - Ischemic heart disease
- Infectious diseases
- Coxsackie B virus
- Chagas disease
- Rheumatic heart disease
- HIV - Systemic disorders
- Sarcoidosis
- Late hemochromatosis
- SLE - Malnutrition
- Thiamine deficiency (wet beriberi)
- Selenium deficiency - Toxic substances
- Cocaine
- Alcohol
- Cardiotoxic drugs (e.g., doxorubicin, daunorubicin, AZT, trastuzumab)
- Inhalation of organic solvents (eg, glue sniffing) - Peripartum cardiomyopathy
- Chronic tachycardia (e.g., atrial fibrillation)
- Radiation
- Endocrinopathies (e.g., pheochromocytoma, acromegaly, hyperthyroidism)
- Valvular heart disease
- Aortic valve stenosis
- Aortic valve regurgitation
- Mitral valve regurgitation
Alcohol use is the only reversible cause of DCM, if alcohol cessation is started early enough.
Restrictive Cardiomyopathy Etiology
- Mostly idiopathic
- Systemic diseases (infiltrative cardiomyopathy)
- Amyloidosis (most common cause)
- Sarcoidosis
- Hemochromatosis (more commonly causes DCM)
- Systemic sclerosis - Other causes
- Löffler endocarditis → a condition characterized by eosinophilic infiltration of endocardium and myocardium occurring in diseases accompanied by eosinophilia (eosinophilia can be caused by different predisposing conditions (e.g., hypereosinophilic syndrome, parasitic infection, eosinophilic leukemia))
- Endocardial fibroelastosis → a condition characterized by diffuse thickening of the left ventricular endocardium due to proliferation of fibrous and elastic tissue. Most commonly occurs in the first 2 years of life. Can be primary (with unknown etiology) or secondary (associated with various congenital heart conditions such as aortic stenosis, aortic atresia, coarctation of the aorta, patent ductus arteriosus).
- Endomyocardial fibrosis → a disorder with unknown etiology characterized by focal or diffuse endomyocardial thickening. Occurs mainly in tropical countries with a low standard of health care. Affects mainly children and adolescents. Proposed causative factors include the following: - Exposure to earth element cerium
- Chronic eosinophilia
- Viral and parasitic infections
- Magnesium deficiency
- Iatrogenic causes of myocardial fibrosis - Chemotherapy → anthracyclines (e.g. doxorubicin), alkylating agents (e.g. carboplatin, cisplatin), tyrosine kinase inhibitors (e.g. imatinib, sorafenib), monoclonal antibodies (e.g., trastuzumab)
- Radiation of the chest
- Open heart surgery
Hypertrophy Cardiomyopathy Physical Examination
- Systolic ejection murmur (crescendo-decrescendo) (caused by dynamicLV outflowtract obstruction due to asymmetrically thickened myocardium)
- Increases with Valsalva maneuver, standing, inotropic drugs (e.g., digitalis) (a decrease in preloaddue to a decrease in venous return to the heart leads to increased force of contraction, which generates stronger forces driving LV outflow obstruction)
- Decreases with hand grip, squatting, or passive leg elevation and drugs that decrease cardiac contractility (e.g., beta blockers) - Possible holosystolic murmur from mitral regurgitation
- Sustained apex beat
- S4 gallop
- Paradoxical split of S2 (audible during expiration but not inspiration)
- Pulsus bisferiens → LV outflow obstruction causes a sudden quick rise of the pulse followed by a slower longer rise (biphasic pulse).
High-Output Heart Failure Etiology
Physiological causes
- Pregnancy
- Fever
- Exercise
Other causes
- Anemia
- Systemic arteriovenous fistulas (e.g., Paget disease of bone) (blood is shunted from the arterial high-pressure system to the venous low-pressure system. This decreases systemic vascular resistance, which in turn increases heart rate, stroke volume, and subsequently cardiac output)
- Hyperthyroidism
- Wet beriberi (vitamin B1 deficiency)
- Sepsis
- Multiple myeloma
- Glomerulonephritis
- Polycythemia vera
- Carcinoid heart disease
Hypovolemic Shock Etiology
Hemorrhage
- Blunt/penetrating trauma (e.g., pelvic ring/femur fractures)
- Upper GI bleeding (e.g., variceal bleeding)
- Postpartum hemorrhage
- Ruptured aneurysm or hematoma
- Arteriovenous fistula
Nonhemorrhagic fluid loss (usually results in dehydration as a result of free water loss. Severe dehydration can result in intravascular volume depletion and hypovolemic shock)
- GI loss → diarrhea, vomiting
- Increased insensible fluid loss (e.g., burns, Stevens-Johnson syndrome)
- Third space fluid loss (e.g., bowel obstruction)
- Renal fluid loss (e.g., adrenal insufficiency, drug-induced diuresis)
Hypovolemic Shock Clinical Features
Loss of intravascular fluid volume → ↓ CO and PCWP → compensatory ↑ SVR
- Weak pulse, tachycardia, tachypnea
- Hypotension
- Physical examination might show:
1. Cold, clammy extremities, slow capillary refill
2. Decreased skin turgor, dry mucous membranes
3. Nondistended jugular veins (↓ CVP)
4. Findings related to the underlying disease → e.g., bleeding, melena, hematemesis, diarrhea - Pulmonary artery catheterization
1. ↓ PCWP (< 15 mmHg) (preload)
2. ↓ CO
3. ↑ SVR (afterload)
Hypovolemic Shock Treatment
Fluid resuscitation
In the case of hemorrhage:
- Hemostasis
- Possibly blood transfusion in a 3:1 (fluid-to-blood) ratio (blood transfusion in addition to fluid resuscitation is required if more than 30% of blood volume (> 1500 mL in a 70 kg male) is lost)
Hypovolemic Shock Complications
Acute renal failure
Cardiogenic Shock Etiology
- Myocardial infarction (MI) is the most common cause.
- Arrhythmias
- Heart failure
- Cardiomyopathy
- Myocarditis
- Ventricular septal defect, ventricular rupture
- Severe aortic or mitral regurgitation
- Certain drugs (e.g., beta blockers, calcium channel blockers)
- Blunt cardiac trauma
Cardiogenic Shock Clinical Features
- Weak pulse, tachycardia
- Hypotension
- Dyspnea
- Mental status change
- Other clinical features related to the underlying disease:
1. Chest pain in MI
2. Palpitations, syncope in arrhythmias
Physical examination might show:
- Cold, clammy extremities, poor capillary refill
- Abnormal auscultatory findings (e.g., S3, S4)
- Pulmonary edema, diffuse lung crackles (fine basal crepitations) (dyspnea and crepitations can also occur with septic shock as a result of ARDS. However, dyspnea and basal crepitations occur early in the case of cardiogenic shock and coarse, diffuse crepitations are heard in the case of ARDS)
- Elevated JVP and distended neck veins (↑ CVP)
Pulmonary artery catheterization → to monitor hemodynamic parameters as a guide to therapy
- ↑ PCWP (> 15 mmHg), can also be ↓
- ↓ CO
- ↑ SVR
Cardiogenic Shock Treatment
Based on the underlying cause
- Cardiopulmonary resuscitation if necessary
- Fluid bolus only in cases of decreased blood pressure and/or PCWP < 15 mmHg (in cardiogenic shock due to left ventricular failure, fluid therapy can be harmful because additional fluid loading may worsen the already increased central vein pressure and existing pulmonary edema without any benefit to cardiac output)
- Inotropic therapy → to maintain perfusion
1. Dopamine in patients with low blood pressure
2. Dobutamine in patients with normal blood pressure - Vasopressors → norepinephrine
- Intra-aortic balloon pump if medical therapy fails
- Diuresis (can be used in the case of fluid overload once cardiac output has been stabilized)
- Treat the underlying cause (e.g., revascularization in MI)
Cardiogenic Shock Complications
Pulmonary edema
Acute renal failure
Obstructive Shock Etiology
- Impairment of diastolic filling of the right ventricle
- Cardiac tamponade
- Constrictive pericarditis
- Restrictive cardiomyopathy - Obstruction of venous return
- Tension pneumothorax
- Intrathoracic tumor - ↑ Ventricular afterload
- Massive pulmonary embolism (PE)
- Aortic dissection
- Aortic stenosis
- Large systemic emboli
- Severe pulmonary hypertension
Obstructive Shock Clinical Features
Obstruction of the heart or its great vessels → inability of the heart to circulate blood → ↓ CO → compensatory ↑ SVR
Similar to hypovolemic shock
- Weak pulse, tachycardia
- Hypotension
- Other clinical features related to the underlying disease → chest pain in PE
- Physical examination might show:
- Cold, clammy extremities
- Poor capillary refill
- Elevated JVP and distended neck veins (↑ CVP)
Pulmonary artery catheterization → to monitor hemodynamic parameters as a guide to therapy
- ↓ PCWP, except for cardiac tamponade
- ↑ PCWP in cardiac tamponade
- Elevation and equalization of pressures in all the cardiac chambers differentiates cardiac tamponade from other causes of cardiogenic shock. - Normal or ↓ CO
- ↑ SVR
Obstructive Shock Treatment
Based on the underlying cause
- Cardiac tamponade → pericardiocentesis
- Pulmonary embolus → thrombolysis
- Tension pneumothorax → needle decompression followed by chest tube insertion
Obstructive Shock Complications
Acute renal failure
Distributive Shock
Redistribution of body fluid due to vasodilation with/without capillary leakage → redistribution of fluid from the intravascular to the extravascular compartment
Types of distributive shock
- Septic shock (most common)
- Neurogenic shock
- Anaphylactic shock
Septic Shock Clinical Features
Dysregulated host response to infection → capillary leakage, systemic vasodilation → acute and life-threatening organ dysfunction
- Fever is typical, but patients may be normothermic or hypothermic (hypothermia is associated with worse clinical outcomes)
- Tachycardia
- Hypotension with a wide pulse pressure
- Other clinical features related to the underlying disease → cough in pneumonia, neck stiffness in meningitis
Physical examination might show:
- Initially flushed, warm skin (later → cold, pale skin)
- Normal capillary refill initially
- Prolonged capillary refill when shock progresses
↑ Lactate (correlates with severity of shock)
Pulmonary artery catheterization
- ↓ PCWP (< 15 mmHg)
- ↑ CO
- ↓ SVR
- ↓ CVP
Septic Shock Treatment
- Fluid resuscitation (required until CVP > 8)
- Vasopressors → in patients refractory to fluids
1. First-line → norepinephrine
2. Second-line → epinephrine - Treat the underlying cause
- Early initiation of broad-spectrum empirical antibiotic therapy (blood cultures should be taken before initiating antibiotic therapy)
- Surgical therapy may be required in some cases (e.g., peritonitis, necrotizing fasciitis)
Septic Shock Complications
Acute renal failure
Anaphylactic Shock Etiology
- Drug reactions (e.g., sulfa drugs)
- Insect stings or bites (e.g., bee stings)
- Food allergies (e.g., peanuts)
- Contrast medium allergy
Anaphylactic Shock Clinical Features
Immunologic anaphylaxis (type I hypersensitivity reaction; IgE-mediated) or nonimmunologic anaphylaxis (not IgE-mediated) → degranulation of mast cells → massive histamine release → systemic vasodilation and increased capillary leakage
Rapid onset of symptoms (minutes to hours)
- Tachycardia, tachypnea
- Hypotension
- Flushed, itchy skin (often hives)
- Bronchospasm, laryngeal edema → wheeze, stridor, dyspnea, cyanosis
- Swelling of conjunctiva, lips, tongue and/or uvula
- Angioedema
- Vomiting, diarrhea
Pulmonary artery catheterization
- ↓ PCWP (< 15 mmHg)
- ↑ CO
- ↓ SVR
Anaphylactic Shock Treatment
- Fluid resuscitation
- Epinephrine (1:1000 IM)
- Adjunctive therapy to epinephrine
- H1/H2 antihistamines
- Glucocorticoids (e.g., hydrocortisone)
Anaphylactic Shock Complications
Airway obstruction
Cardiovascular collapse
Neurogenic Shock Etiology
- Spinal cord injury (the loss of sympathetic tone and thus neurogenic shock is most common with spinal cord injuries above the level of T6)
- Traumatic brain injury
- Cerebral hemorrhage
- Neuraxial anesthesia
Neurogenic Shock Clinical Features
Damage of autonomic pathways → loss of sympathetic vascular tone → unopposed vagal tone → peripheral vasodilation → pooling of peripheral blood
- Bradycardia
- Hypotension
- Flushed, warm skin
- Other clinical features related to the underlying disease → neurological deficits (e.g., flaccid paralysis in spinal trauma)
Pulmonary artery catheterization
- ↓ PCWP (< 15 mmHg)
- ↓ CO
- ↓ SVR
- ↓ CVP
Neurogenic Shock Treatment
- Fluid resuscitation
- Atropine or pacing to treat bradycardia
- Vasopressors → if fluid resuscitation fails to increase MAP beyond 90 mmHg
- Normal heart rate → phenylephrine
- If heart rate < 60/min → epinephrine
Cardiac Tamponade / Pericardial Effusion Etiology
Hemopericardium
- Cardiac wall rupture (e.g., complication of myocardial infarction)
- Chest trauma
- Aortic dissection
- Cardiac surgery (e.g., heart valve surgery, coronary bypass surgery)
Serous or serosanguinous pericardial effusion
- Idiopathic
- Acute pericarditis (especially viral, but also fungal, tuberculous or bacterial)
- Malignancy
- Postpericardiotomy syndrome
- Uremia
- Autoimmune disorders
- Hypothyroidism
Beck Triad
Hypotension
Muffled heart sounds
Distended neck veins (due to elevated jugular venous pressure)
Seen in cardiac tamponade
Cardiac Tamponade Clinical Findings
Beck triad (hypotension, muffled heart sounds, distended neck veins (due to elevated jugular venous pressure)) Tachycardia Pulsus paradoxus
Echocardiography
- Indication → all patients with suspected pericardial effusion
- Procedure → transthoracic echocardiographt (TTE) (gold standard)
- Allows for the detection of:
1. Small effusions of 25–50 mL during ventricular systole
2. Effusions of > 50 mL throughout the cardiac cycle
3. Cardiac tamponade - Findings supportive of cardiac tamponade
1. Chamber collapse - During a normal cardiac cycle, pressure inside the chambers varies between the chambers and within the cardiac cycle. In tamponade, as pressure from the effusion increases, intrapericardial pressure exceeds intracardiac pressure, and the chambers collapse in a predictable order
- Early signs → collapse of the right atrium during systole, collapse of the right ventricle during early diastole
- Later → collapse of the left atrium (specificity 98% for cardiac tamponade)
- Rare → collapse of the left ventricle
2. Swinging motion of the heart (due to fluid in the pericardial space) - Inspiration → decrease in LV filling (↑ venous return → ↑ right ventricular filling → ↓ left ventricular filling)
- Exhalation → increase in LV filling and decrease in RV filling
ECG
- Sinus tachycardia
- Low voltage QRS complexes
- Electrical alternans → consecutive QRS complexes that alternate in height due to the swinging motion of the heart when surrounded by large amounts of pericardial fluid
- Pulseless electrical activity (PEA) in cardiac arrest (this is a form of pseudo-PEA in which, unlike true PEA, myocardial contractions might be observed on echocardiogram. The pressure of the effusion on the heart causes ventricles to collapse, leading to insufficient cardiac output to generate a palpable pulse)
Transudate Pericardial Fluid Etiology
- Heart Failure
- Renal Failure
- Hypoalbuminemia
- Postradiotherapy
Exudate Pericardial Fluid Etiology
- Viral infection
- Inflammation (may occur after myocardial infarction)
- Malignancy
- Autoimmune disease
- Chylopericardium
Hemorrhagic Pericardial Fluid Etiology
- Postcardiac surgery
- Cardiac rupture
- Aortic dissection
- Tuberculosis
- Malignancy (more commonly caused by metastatic disease (in particular, lymphomas, leukemias, melanoma, lung cancer, and breast cancer) than primary malignancies)
Purulent Pericardial Fluid Etiology
Tuberculosis
Bacterial infection
Ewart Sign
Dullness to percussion at the base of the left lung with increased vocal fremitus and bronchial breathing due the compression of lung parenchyma by the pericardial effusion
Seen in pericardial effusion
Pericardial Effusion Clinical Findings
Shortness of breath, especially when lying down (orthopnea)
Retrosternal chest pain
Can cause compressive symptoms
- Hoarseness (due to compression of the laryngeal nerve)
- Nausea (due to compression of the diaphragm)
- Dysphagia (due to compression of the esophagus)
- Hiccups (due to compression of the phrenic nerve)
Apical impulse is difficult to locate or nonpalpable.
Ewart sign → dullness to percussion at the base of the left lung with increased vocal fremitus and bronchial breathing due the compression of lung parenchyma by the pericardial effusion
Echocardiography
- Findings supportive of pericardial effusion
1. Anechoic space between the pericardium and epicardium (volume can be assessed by measuring the distance between the pericardiallayers)
2. Hemorrhagic or purulent effusions may be echogenic.
ECG
- Findings in pericardial effusion
1. Normal in smaller effusions
2. Low voltage complexes and electrical alternans in larger effusions
Chest x-ray is not required to diagnose pericardial effusion but often performed to exclude other causes of dyspnea
- PA view findings
1. Normal in small effusions (on a PA view x-ray, the pericardial effusion must be > 250–300 mL to alter the cardiac silhouette)
2. Enlarged cardiac silhouette and clear lungs may be seen in moderate effusions.
3. Water bottle sign → the radiographic sign of a large pericardial effusion in which the cardiac silhouette resembles a bottle - Lateral view findings
1. Posterior inferior bulge sign → a change in the silhouette of the heart due to a pericardial effusion that collects in the posterior-inferior pericardiac recess and expands the pericardium
2. Pericardiac fat pad sign → a > 2 mm soft-tissue stripe between the epicardiac fat and the anterior mediastinal fat that may be visible anterior to the heart
Pulsus Paradoxus
Pathological decrease in the pulse wave amplitude and systolic blood pressure > 10 mm Hg during inspiration (although the pulse wave physiologically decreases slightly during inspiration, this cannot be detected by palpation of the artery)
The difference between the systolic pressure at which Korotkoff sounds first become audible during expiration and the pressure at which they are heard throughout all phases of respiration quantifies pulsus paradoxus.
Possible causes:
- Constrictive pericarditis
- Cardiac tamponade
- Severe obstructive airway disease (asthma, COPD)
- Obstructive sleep apnea
- Croup
- Tension pneumothorax
- Superior vena cava syndrome
Cardiac Tamponade Treatment
In cardiac tamponade, the mainstay of treatment is urgent decompression of the heart.
- Urgent pericardiocentesis
- Hemodynamically unstable → without imaging guidance (blind pericardiocentesis can be performed using landmarks but there is a risk of perforating the lung, liver, internal thoracic artery, colon, stomach, ventricle, or left anterior descending artery)
- Hemodynamically stable → ultrasound, CT, or fluoroscopy guidance - Hemodynamic support
- Cautious fluid resuscitation (only in hypovolemic patients) (excessive fluid volume will increase pericardial pressure and exacerbate tamponade physiology)
- Inotropic support → dobutamine (of theoretical benefit, because endogenous catecholamine release is already high)
- Avoid anesthetic agents and positive pressure ventilation (decreased venous return as a result of general anesthetic agents, as well as positive pressure ventilation, can cause catastrophic hypotension in patients with cardiac tamponade) - Subsequent management
- Surgical management if the tamponade immediately reaccumulates, pericardiocentesis is unsuccessful, or conditions make pericardiocentesis difficult (there is often no benefit to pericardiocentesis in aortic dissection or myocardial rupture, because the free communication between the aorta and ventricle means that the pericardium will immediately refill; patients require immediate surgical treatment of the underlying cause. A pericardial window or pericardiotomy may be required in conditions such as loculated effusions and clotted hemopericardium, where pericardiocentesis is unlikely to be successful)
- Identify and treat the underlying cause.
Endocarditis Risk Factors
- Male sex
- Age > 60 years
- Cardiac conditions
1. Acquired valvular disease (e.g., rheumatic heart disease, aortic stenosis, degenerative valvular disease)
2. Prosthetic heart valves
3. Congenital heart defects (e.g., VSD, bicuspid aortic valve)
4. Previous IE - Noncardiac risk factors
1. Poor dental status
2. Dental procedures
3. Nonsterile venous injections (e.g., in IV drug use)
4. Intravascular devices
5. Surgery
6. Chronic hemodialysis
7. Immunocompromise (e.g., HIV infection, diabetes)
8. Other bacterial infections (e.g., UTIs, spondylodiscitis, periodontal infection)
Endocarditis Main Pathogens
- Staphylococcus aureus
- Approx. 35 – 40% of native valve IE cases
- Most common cause of acute IE, including IV drug users and patients with prosthetic valves or pacemakers/ICDs
- Typically affects healthy valves.
- Usually fatal within 6 weeks if left untreated - Viridans streptococci
- Approx. 20% of native valve IE cases
- Most common cause of subacute IE, especially in predamaged native valves (mainly the mitral valve)
- Common cause of IE following dental procedures
- Produce dextrans that facilitate binding of fibrin-platelet aggregates on heart valves - Staphylococcus epidermidis
- Less than 15% of native valve IE cases
- Bacteremia from infected peripheral venous catheters (S. epidermis is a skin commensal for which peripheral lines provide an easy port of entry)
- Common cause of subacute IE in patients with prosthetic heart valves, pacemakers, or ICDs - Enterococci (especially Enterococcus faecalis)
- Approx. 10% of native valve IE cases
- Multiple drug resistance (resistant to penicillin G and cephalosporins (intrinsic cephalosporin resistance))
- Common cause of IE following nosocomial UTIs (E. faecalis is a common cause of UTIs, and it is also associated with catheter and pelvic infections)
- Causes native and prosthetic valve IE
- Following gastrointestinal or genitourinary procedures - Streptococcus gallolyticus subsp. gallolyticus (Sgg) (formerly known as Streptococcus bovis biotype I)
- Less than 15% of native valve IE cases
- Associated with colorectal cancer (the colonic tumor provides an entry point for bacteria)
- If Sgg is detected, colonoscopy is indicated. - Gram-negative HACEK group (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)
- Less than 5% of native valve IE cases
- Physiological oral pharyngeal flora
- In patients with poor dental hygiene and/or periodontal infection - Fungal endocarditis (Candida, Aspergillus fumigatus)
- Less than 5% of native valve IE cases
- At risk groups
Immunosuppressed patients (e.g., patients with HIV or organ transplantation)
IV drug abusers
Patients who underwent cardiosurgical interventions
Patients with long-term indwelling IV catheters - Coxiella burnetii and Bartonella species
- Less than 5% of native valve IE cases
- Gram-negative pathogens responsible for culture-negative endocarditis
Acute Bacterial Endocarditis
Acute onset
Rapid, fulminant progression (days to weeks)
Severe constitutional symptoms (e.g., high fever)
Pathogens:
Most common → S. aureus (associated with large vegetations that can destroy the valves) (vegetations are conglomerates of bacteria, platelets, fibrin, and inflammatory cells)
Others → group A hemolytic streptococci, S.pneumoniae, N.gonorrhoeae
Valves affected:
Healthy native valves
Subcute Bacterial Endocarditis
Insidious onset Slow progression (weeks to months) Less severe constitutional symptoms (e.g., low-grade fever, malaise, chills, dyspnea, back pain, weight loss)
Pathogens: Viridans streptococci S. aureus Enterococci HACEK
Valves Affected:
Native valves with prior injury or congenital defects
Prosthetic Valve Endocarditis
Early-onset → ≤ 1 year after surgery
Late-onset → > 1 year after surgery
Pathogens:
Early-onset → Coagulase-negative staphylococci, S. aureus, or gram-negative bacilli (most common)
Late-onset → Coagulase-negative staphylococci, S. aureus, Viridans group streptococci (most common)
Valves Affected:
Mechanical valves
Bioprosthetic valves
Osler Nodes
Painful nodules on pads of the fingers and toes caused by immune complex deposition
Immunologic phenomena seen in infective endocarditis
Roth Spots
Round retinal hemorrhages with pale centers (characterized histologically by microthrombi that form at the site of retinal capillary damage)
Immunologic phenomena seen in infective endocarditis
Janeway Lesions
- Small, nontender, erythematous macules on palms and soles
- Microabscesses with neutrophilic capillary infiltration and areas of hemorrhage caused by septic microemboli from valve vegetations
Vascular phenomena seen in infective endocarditis
Infective Endocarditis Treatment
Empiric treatment
- The goal is to providebroad-spectrumcoverage for possible resistant bacteria.
- Indicated for hemodynamically unstable patients
- Consider for hemodynamically stable patients with acute symptoms and/or complications (empiric therapy may not be required in stable patients without complications)
- Take the following into account when choosing an agent:
1. Patient-related factors
2. Disease-related factors
3. Local and individual flora and resistance patterns - Common regimens (these frequently include drugs that have significant side effects (e.g., AKI, ototoxicity))
- Native valve endocarditis → vancomycin PLUS beta-lactam (e.g., ceftriaxone, cefepime) (this covers the most common gram-positive organisms (e.g., staphylococci, streptococci, enterococci) and provides some gram-negative coverage)
- Prosthetic valve endocarditis → add gentamicin PLUS rifampin to vancomycin PLUS beta-lactam (if ≤ 1 year after placement) (because of the high mortality rates in patients with MRSA prosthetic valve endocarditis, combination therapy is used (especially with rifampin) to ensure complete sterilization of the foreign body)
Targeted antibiotics (adapted according to culture results)
- Recommended for all patients (some stable patients with no complications can forego empiric antibiotics and begin targeted antibiotics after culture results are available)
- Duration of therapy → variable; can be ≥ 2–6 weeks after the first sterile blood culture
- Staphylococci
1. Methicillin-susceptible staphylococci (e.g., MSSA) → antistaphylococcal beta-lactams (e.g., nafcillin, oxacillin) (these antibiotics have been found to be superior in targeting MSSA than vancomycin)
2. Methicillin-resistant staphylococci (e.g. MRSA) → vancomycin
3. Prosthetic valve endocarditis (≤ 1 year after placement) → add gentamicin PLUS rifampin to regimen (because of the high mortality rates in patients with MRSA prosthetic valve endocarditis, combination therapy is used (especially with rifampin) to ensure complete sterilization of the foreign body.) - Viridans group streptococci → beta-lactams (e.g., penicillin G, ampicillin)
- Enterococci → combination therapy (e.g., ampicillin PLUS gentamicin)
- HACEK → ceftriaxone (first-line)
Infective Endocarditis Prophylaxis
Common indications
- Prior to the implantation of cardiac implantable electronic devices (e.g., AICD)
- Some dental procedures (i.e., those involving perforation of the oral mucosa or manipulation of gingival tissue and/or periapical region of teeth) in patients with high-risk cardiac features, such as:
- Prosthetic heart valves or prosthetic material used for valve repair
- History of endocarditis
- Types of congenital heart disease
Common regimens (usually administered 30–60 minutes prior to the procedure)
- Prior to cardiac device implantation → cefazolin
- Prior to dental procedures
- No penicillin allergy → amoxicillin OR ampicillin
- Penicillin allergy → a macrolide (e.g., azithromycin ) OR clindamycin
Noninfective Endocarditis (Nonbacterial Thrombotic Endocarditis)
- Rare, noninfective form of endocarditis due to sterile platelet thrombus formation on the heart valves (usually mitral and aortic valves)
- Libman-Sacks endocarditis is a type of noninfective endocarditis with verrucous vegetations in individuals with systemic lupus erythematosus or antiphospholipid syndrome
Etiology
- Malignancy
- Hypercoagulable states
- Underlying trauma (e.g., from indwelling vascular catheters)
- Previous rheumatic fever
- Autoimmune conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome)
- Chronic infections (e.g., TB, pneumonia, osteomyelitis)
Clinical features
- Valves and cardiac function are rarely impaired.
- Compared to IE, vegetations are easily dislodged and embolization is common, leading to hemorrhages under the nails, skin, and retina
- Most affected individuals are asymptomatic until embolization occurs.
Diagnostics
- Negative blood cultures
- Echocardiography → valve vegetations
- Biopsy (definitive diagnosis)
- Sterile vegetations on either surface of the valve composed of immune complexes, mononuclear cells, and thrombi interwoven with fibrin strands
- Not always feasible, therefore diagnosis is mostly made based on clinical findings, negative blood cultures, echocardiography findings, and no response to antibiotic treatment
Treatment
- Anticoagulation with heparin
- Treatment of the underlying condition
Prosthetic Valve Thrombosis
- Usually affects mechanic valves
- Rare if anticoagulation is adequate
Etiology → insufficient anticoagulatory therapy after valve replacement
Clinical features
- Signs of acute heart failure
- Left heart failure → dyspnea and cough
- Right heart failure → edema and jugular venous distention
- Deterioration of general condition, cardiac arrhythmias, cerebral emboli (stroke)
Diagnostics → transesophageal echocardiography
Treatment
- Anticoagulation and fibrinolysis
- Surgical valve replacement
Aschoff Bodies
- Granuloma of rheumatic inflammation
- Central area of fibrinoid necrosis
- Surrounded by characteristic multinucleated giant cells (Aschoff cells) and other inflammatory cells (mononuclear cells, plasma cells, and T lymphocytes) due to a type IV hypersensitivity reaction (acute rheumatic fever is due to a type II hypersensitivity reaction, but the chronic sequelae of acute rheumatic fever (i.e., rheumatic heart disease) involve a type IV hypersensitivity reaction that is responsible for non-caseating granuloma formation)
Seen in rheumatic fever
Anitschkow Cells
- Cardiac histiocytes (mononuclear cells) appearing in Aschoff bodies
- Large and elongated cells
- Longitudinal section → ovoid nucleus containing wavy, caterpillar-like bar of chromatin (caterpillar cell)
- Transverse section → owl-eye appearance (not to be confused with the owl-eye appearance of inclusion bodies in cytomegalovirus (CMV) infection)
Seen in rheumatic fever
Acute Pericarditis Etiology
- Idiopathic
- Infectious
- Most commonly viral (e.g., coxsackie B virus)
- Bacterial (e.g., Staphylococcus spp., Streptococcus spp., or M. tuberculosis) (causes exudative (serous) pericarditis)
- Fungal
- Toxoplasmosis - Myocardial infarction
- Postinfarction fibrinous pericarditis → within 1–3 days as an immediate reaction
- Dressler syndrome → weeks to months following an acute myocardial infarction - Postoperative (postpericardiotomy syndrome) → blunt or sharp trauma to the pericardium
- Uremia (e.g., due to acute or chronic renal failure)
- Radiation
- Neoplasm (e.g., Hodgkin lymphoma)
- Autoimmune connective tissue diseases (e.g., rheumatoid arthritis, systemic lupus, scleroderma)
Acute Pericarditis Complications
- Constrictive pericarditis (as a complication of acute pericarditis)
- Cardiac tamponade
Constrictive Pericarditis Clinical Presentation
Symptoms of fluid overload (i.e., backward failure)
- Jugular vein distention, ↑ jugular venous pressure
- Kussmaul sign
- Hepatic vein congestion → hepatomegaly, painful liver capsule distention, hepatojugular reflux
- Peripheral edema or anasarca, ascites with abdominal discomfort
Symptoms of reduced cardiac output (i.e., forward failure)
- Fatigue, dyspnea on exertion
- Tachycardia (compensatory mechanism for maintaining cardiac output when stroke volume is reduced)
- Pericardial knock → sudden cessation of ventricular filling during early diastole that is heard best at the left sternal border
- Pulsus paradoxus → ↓ blood pressure amplitude by at least 10 mm Hg during deep inspiration
Constrictive Pericarditis Findings
The diagnosis of constrictive pericarditis is based on characteristic imaging findings (most commonly echocardiography but MRI and CT may be used).
Echocardiography
- ↑ Pericardial thickness (transesophageal echocardiography has greater sensitivity for assessing pericardial thickness than transthoracic echocardiography)
- Abnormal ventricular filling with sudden halt during early diastole
- Variation in ventricular filling with inspiration
- Across the tricuspid valve → the velocity of blood flow increases (due to constriction)
- Across the mitral valve → the velocity of blood flow decreases (due to a decrease in relaxation of the left ventricle) - Moderate biatrial enlargement
- Excludes right ventricular hypertrophy and cardiomyopathy
CT and cardiac MRI
- Pericardial thickening > 2 mm (normal pericardium is < 2 mm thick)
- Calcifications
- Normal cardiac silhouette
Chest x-ray (PA and lateral views)
- Heart size → normal or slightly increased
- Pericardial calcifications
- Clear lung fields
Cardiac catheterization
- Similar pressures in the left and right atria and right ventricle at the end of diastole (e.g., “equalization of pressures”)
- Normal pulmonary artery systolic pressure < 40 mm Hg (this helps to differentiate constrictive pericarditis from restrictive cardiomyopathy)
- Mean right arterial pressure > 15 mm Hg
- Square root sign
- Also known as dip-and-plateau waveform
- Sudden dip in the right and left ventricular pressure in early diastole followed by a plateau during the last stage of diastole (the dip in ventricular pressure indicates rapid early diastolic filling of the ventricles, while the plateau represents the lack of additional filling due to the restriction imposed by the fibrotic pericardium. The pressure tracing looks similar to the radical or square root symbol)
ECG
- No conclusive findings → generalized flat/inverted T waves, low QRS voltage
- Atrial fibrillation can occur in severe disease.
Myocarditis Etiology
Infectious
- Viral (up to 50% of myocarditis cases are classified as idiopathic. In these cases, a viral etiology is suspected, but cannot be sufficiently proven)
- Most commonly implicated → coxsackie B1-B5 (picornavirus), parvovirus B19, human herpesvirus 6 (HHV-6), adenovirus, HCV, HIV
- Other viruses → EBV, CMV, echovirus, H1N1 influenza A (in total, about 20 viruses have been implicated in the etiology of myocarditis) - Bacterial
- Group A β-hemolytic Streptococcus (acute rheumatic fever)
- Corynebacterium diphtheriae (diphtheria)
- Borrelia burgdorferi (borreliosis)
- Mycobacterium (tuberculosis)
- Mycoplasma pneumoniae - Fungal (Candida, Aspergillus)
- Parasitic
- Protozoan → Toxoplasma gondii, Trypanosoma cruzi (Chagas disease, common in South America)
- Helminthic → Trichinella, Echinococcus
Noninfectious
- Connective tissue diseases (e.g., systemic lupus erythematosus, sarcoidosis, dermatomyositis, polymyositis)
- Vasculitis syndromes (e.g., Kawasaki disease)
- Toxic myocarditis
- Toxins (e.g., carbon monoxide poisoning, black widow venom)
- Medication (e.g., sulfonamides), chemotherapy (e.g., anthracycline, doxorubicin)
- Alcohol, cocaine
- Radiation therapy
Myocarditis Complications
- Progression to dilated cardiomyopathy (∼ 15% of cases)
- Heart failure or sudden cardiac death → probably due to ventricular tachycardia or fibrillation (common in adults < 40 years old)
- Acute and/or persistent arrhythmias
- Atrioventricular block
- Intracardiac thrombi formation, which can result in systemic embolization
- Concurrent pericarditis (perimyocarditis) that may lead to cardiac tamponade (associated with large pericardial effusions)
Myocarditis Prognosis
- Viral myocarditis → most adults make a full recovery; however, progression to dilated cardiomyopathy may occur.
- However, prognosis is very poor for infants (75% lethality rate).
- Lethality rate for children is 25% and another 25% may develop chronic heart failure complications.
Markers of poor prognosis
- Poor ventricular function, left bundle-branch block, low ejection fraction
- Persistent viral genome (in the myocardium)
- Persistent, chronic myocarditis
Giant Cell Arteritis Complications
- Permanent vision loss → ∼ 20–30% if giant cell arteritis is left untreated (early administration of high-dose glucocorticoids significantly lowers the risk of visual complications)
- Cerebral ischemia (e.g., transient ischemic attack and stroke) → < 2% of cases (predominantly in the area of the posterior cerebral artery)
- Aortic aneurysm and/or dissection → ∼ 12% of patients (routine screening (e.g., serial chest x-ray or CT scans) is not generally recommended)
Giant Cell Arteritis Pathology
- Panarteritis of the large and medium-sized arteries
- Proliferation of the intima (and subsequent stenosis of the artery)
- Necrosis of the media
- Fragmentation of the internal elastic lamina
- Predominantly mononuclear infiltration of the vessel wall with formation of giant cells (giant cells are formed through the fusion of several other cells. Therefore, they contain multiple nuclei. They are usually seen in giant cell arteritis but may not be present in all cases)
Takayasu Arteritis (Aortic Arch Syndrome) Diagnosis
A diagnosis requires three or more of the following diagnostic criteria to be fulfilled:
- Age of onset → ≤ 40 years
- Claudication of upper or lower extremities while in use
- Audible bruit over the subclavian artery or abdominal aorta
- Decreased brachial artery pulse
- Blood pressure difference > 10 mm Hg between arms
- Abnormal arteriography of the aorta or large blood vessels in the extremities that is not due to arteriosclerosis or fibromuscular dysplasia
Biopsy of the affected vessel
- Granulomatous thickening of the aortic arch
- Plasma cells and lymphocytes in media and adventitia
- Vascular fibrosis
Laboratory findings → ↑ ESR
Angiography (gold standard) → detects vascular stenosis (angiography is considered the gold standard for diagnosis and monitoring of disease activity. There is some evidence that noninvasive imaging (e.g., ultrasonography, MRI, 18F-FDG-PET) may allow for earlier diagnosis than angiography)
Takayasu Arteritis (Aortic Arch Syndrome) Presentation
Fever, malaise, arthralgia, night sweats (a long history of nonspecific symptoms is common)
Vascular symptoms
- Decreased bilateral brachial and radial pulses (so-called pulseless disease)
- Syncope, angina pectoris
- Bilateral carotid bruits
- Impaired vision
- Movement-induced muscular pain in one or more limbs
- Raynaud phenomenon
- Hypertension (due to renal artery stenosis)
Skin manifestations
- Erythema nodosum
- Urticaria
Kawasaki disease (Mucocutaneous lymph node syndrome) Presentation
Specific symptoms include:
- Erythema and edema of hands and feet, including the palms and soles (the first week)
- Possible desquamation of fingertips and toes after 2–3 weeks
- Polymorphous rash, originating on the trunk
- Painless bilateral “injected” conjunctivitis without exudate (more pink than red)
- Oropharyngeal mucositis
- Erythema and swelling of the tongue (strawberry tongue)
- Cracked and red lips - Cervical lymphadenopathy (mostly unilateral)
Nonspecific symptoms may precede the onset of Kawasaki disease (e.g., diarrhea, fatigue, abdominal pain)
Always consider Kawasaki disease in small children with a rash and high fever unresponsive to antibiotics.
Polyarteritis Nodosa (PAN) Presentation
- Nonspecific symptoms
- Fever, weight loss, malaise
- Muscle and joint pain (PAN may involve various organs and there is no symptom that is pathognomonic for PAN. A high index of suspicion is required to diagnose it correctly) - Renal involvement (∼ 60%) → hypertension, renal impairment
- Coronary artery involvement (∼ 35%); increased risk of myocardial infarction
- Skin involvement (∼ 40%) → rash, ulcerations, nodules
- Neurological involvement → polyneuropathy (mononeuritis multiplex), stroke
- GI involvement → abdominal pain, melena, nausea, vomiting
- Usually spares the lungs (helps to differentiate from other forms of vasculitis)
Polyarteritis Nodosa (PAN) Findings
- Blood tests
- Serology → hepatitis B, hepatitis C
- ↑ ESR
- Anemia, leukocytosis
- ANCA-negative (positive p-ANCA in15–30% of cases) - Urine analysis → proteinuria, hematuria
- Muscle biopsy
- Transmural inflammation of the arterial wall with leukocytic infiltration and fibrinoid necrosis (in two-thirds of cases, arterial inflammation is observed in the entire musculoskeletal system. In order to obtain the highest diagnostic yield, biopsy material should be taken from the affected regions, primarily tender muscles)
- The inflammatory lesions are usually in various stages of development and regeneration. - Angiography
- Numerous small aneurysms and stenosis of small and medium-sized vessels of the involved organs (string of pearls appearance)
- Most commonly seen in the renal arteries (pulmonary arteries are usually not affected) (angiography is indicated if involved tissue is not easily accessible for biopsy)
Kawasaki disease (Mucocutaneous Lymph Node Syndrome) Treatment
- IV immunoglobulin (IVIG)
- High single-dose to reduce the risk of coronary artery aneurysms
- Most effective if given within the first 10 days following disease onset - High-dose oral aspirin (initial high doses of aspirin are given for the anti-inflammatory effect until the fever has subsided. Treatment is then continued with a lower dosage for its antiplatelet effect until ESR has normalized (1–2 months). Kawasaki disease is a rare exception to the contraindication of giving children aspirin, which is associated with Reye syndrome)
- IV glucocorticoids → may be considered in addition to standard treatment, esp. in cases of treatment-refractory disease, as they lower the risk of coronary involvement
Kawasaki disease (Mucocutaneous Lymph Node Syndrome)
- Coronary artery aneurysm (the risk of developing coronary artery aneurysm in untreated patients is 25%)
- The risk of aneurysms is highest during the second and third weeks following symptom onset.
- Rupture or thrombosis of the aneurysm can be lethal. - Myocardial infarction
- Myocarditis
- Arrhythmias
Buerger Disease (Thromboangiitis Obliterans) Presentation
Early manifestations
- Superficial thrombophlebitis (which is often migratory) with tender nodules along the course of the vein (superficial thrombophlebitis is the result of superficial vein involvement and is often seen prior to the onset of limb ischemia. Superficial thrombophlebitis is a clinical manifestation which distinguishes TAO and Behçet disease from other forms of vasculitis)
- Intermittent claudication (intermittent claudication in the case of TAO is usually limited to the feet, calves, and/or hands)
- Raynaud disease
Late manifestations (occur as a result of critical limb ischemia)
- Rest pain
- Cool peripheral extremities
- Trophic nail changes
- Ulceration and/or gangrene of fingertips and/or toes (digits may autoamputate)
- Normal brachial and popliteal pulses but poor/absent radial, ulnar, anterior tibial, posterior tibial, and/or dorsal pedis pulsations (abnormal Allen test may be seen if the ulnar artery is involved)
Buerger Disease (Thromboangiitis Obliterans) Findings
Laboratory findings
- ESR and CRP are within normal limits (unlike other vasculitides where ESR and/or CRP may be elevated)
- Autoantibodies (e.g., ANA, RF) are absent and a hypercoagulability screen is normal
- Ankle-brachial index → decreased (however, the presence of a normal ankle-brachial index does not rule out TAO)
Arteriography
- Imaging modality of choice
- Shows non-atherosclerotic, smooth, tapering, segmental lesions that occlude distal vessels of extremities with corkscrew-shaped collateral vessels around the site of occlusion (the corkscrew collaterals are actually dilated vasa vasora of the occluded artery. The findings on arteriography are not pathognomonic for TAO and can be seen in other peripheral artery diseases that affect small and medium-sized arteries of upper and lower limbs)
Biopsy → although confirmation of the diagnosis requires excisional skin biopsy, biopsies are rarely performed.
Contiguous extension of the inflammatory process to the adjacent vein and nerve, resulting in the encasement of the artery, vein, and nerve in a fibrous sheath (contiguous extension to veins is uncommon in other forms of vasculitis)
Behcet Syndrome (Silk Road Disease) Etiology
- Autoimmune and infectious triggers (e.g., precipitating HSV or parvovirus infection) have been suggested.
- Strong HLA-B51 association
Behcet Syndrome (Silk Road Disease) Presentation
- Recurrent painful oral aphthous ulcers (95–100%)
- Usually last about 1–4 weeks
- Typically the initial presenting symptom - Recurrent genital ulcerations (60–90%)
- Single or multiple ulcers that resemble oral aphthous ulcers and heal with scarring
- Most commonly affect the vulva in female and the scrotum in male individuals - Ocular disease (50–80%) (initial presenting feature of Behcet disease in 10–20% of cases)
- Uveitis (iridocyclitis, chorioretinitis), keratitis, and/or retinal vasculitis
- Typically bilateral
- More common and more severe among men
- Usually occurs 2–3 years after the onset of oral and/or genital ulcers - Skin lesions (35–85%)
- Erythema nodosum
- Papulopustular lesions
- Pyoderma gangrenosum
- Pseudofolliculitis or acneiform eruptions
- Dermatographism → formation of urticaria after minor pressure is applied to the skin, likely mediated by local histamine release - Arthritis (30–70%)
- Non-erosive, non-deforming, asymmetric mono-/oligoarthritis
- Usually affects the knees, ankles, hands, and/or wrists (the axial skeleton, more proximal joints such (e.g., hips, shoulder), and more distal joints (e.g., interphalangeal joints) are usually not affected. Arthritis that predominantly affects these joints suggests a different cause) - Gastrointestinal disease → ileocecal ulceration with abdominal pain, anorexia, diarrhea, lower GI bleeding, nausea, vomiting (gastrointestinal disease is more common in Japan and Korea. In Behcet disease, gastrointestinal lesions usually appear 4–6 years after the onset of oral ulcers)
- Vasculopathy (although Behcet disease can affect both arteries and veins, the veins are affected more commonly than the arteries)
- Superficial thrombophlebitis
- Thrombosis of large veins (e.g., deep vein thrombosis, Budd-Chiari syndrome)
- Arterial thrombosis
- Aneurysms (e.g., pulmonary artery aneurysms) (only systemic vasculitis known to cause pulmonary artery aneurysms) - Neuro-Behcet syndrome (5–10%) (neurological symptoms usually occur within 5 years of disease onset)
- Parenchymal CNS disease → behavioral changes, ataxia, hemiparesis, sudden hearing loss (vasculitis within the CNS can cause unifocal or multifocal parenchymal damage. The brain stem is often affected)
- Extra-parenchymal CNS disease → cerebral venous thrombosis, intracranial hypertension
Cutaneous Small Vessel Vasculitis (Hypersensitivity Vasculitis) Etiology
- Drug-induced (e.g., PTU, hydralazine, allopurinol, penicillins, cephalosporin, sulfasalazine, phenytoin)
- Infections (e.g., HIV, HCV)
Cutaneous Small Vessel Vasculitis (Hypersensitivity Vasculitis) Presentation
Symptoms usually occur 7–10 days after drug exposure.
- Painful, palpable purpura
- Other skin lesions may occur → subcutaneous nodules, chronic urticaria, ulcers, vesicles
Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) Findings
- Peripheral blood eosinophilia
- ↑ IgE level
- Circulating MPO-ANCA/pANCA (∼ 40% of cases)
- Biopsy (confirmatory test) (from any affected tissue (e.g., nerves, lung, kidneys, skin))
1. Tissue eosinophilia
2. Necrotizing vasculitis, and necrotizing granuloma
Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) Clinical Features
- Severe allergic asthma attacks (chief complaint)
- Allergic rhinitis/sinusitis
- Skin nodules, palpable purpura
- Pauci-immune glomerulonephritis
- CNS → impaired mental status
- Mononeuritis multiplex (loss of motor and sensory function, with wrist or foot drop), symmetric or asymmetric polyneuropathy
- Pericarditis
- Gastrointestinal involvement → bleeding, ischemia, perforation
Granulomatosis with Polyangiitis (Wegener Granulomatosis) Presentation
Constitutional symptoms → fever, night sweats, weight loss, arthralgias
ENT involvement → often the first clinical manifestation
- Chronic rhinitis/sinusitis → nasopharyngeal ulcerations → nasal septum perforation → saddle nose deformity (depression of the nasal dorsum)
- Chronic otitis and/or mastoiditis
- In some cases, thick, purulent discharge, sometimes containing blood
- Oral ulcers
- Gingival hyperplasia (strawberry gingivitis)
Lower respiratory tract → potentially life-threatening
- Treatment-resistant, pneumonia-like symptoms with cough, dyspnea, hemoptysis, wheezing, hoarseness, and/or pleuritic pain
- Clinical features of pulmonary fibrosis, pulmonary hypertension, and/or pulmonary hemorrhage may occur.
Renal involvement → potentially life-threatening
- Pauci-immune glomerulonephritis (pauci‑immune indicates that there is little evidence of immune complex/antibody deposits) → rapidly progressive (crescentic) glomerulonephritis (RPGN) with possible pulmonary-renal syndrome
- Typically causes hematuria and red cell casts
Skin lesions
- Papules, vesicles, ulcers
- Purpura of the lower extremities
- May lead to necrotizing vasculitis of small vessels → dry gangrene of digits
Ocular involvement
- Conjunctivitis, episcleritis, retinal vasculitis
- Corneal ulcerations
Cardiac involvement → potentially life-threatening
- Pericarditis, myocarditis
- Vasculitis of the coronary arteries; may lead to myocardial infarction and death
- Rarely → cardiomyopathy
Upper respiratory manifestations (i.e., purulent, sometimes bloody discharge, chronic nasopharyngeal infections, saddle nose deformity) are the most common chief complaints.
GPA triad → necrotizing vasculitis of small arteries, upper/lower respiratory tract manifestations, and glomerulonephritis.
Granulomatosis with Polyangiitis (Wegener Granulomatosis) Findings
Laboratory analysis
- ↑ Creatinine and ↑ BUN
- ↑ ESR and ↑ CRP
- Evidence of PR3-ANCA/c-ANCA (anti-proteinase 3) → highly sensitive and positive in ∼ 90% of patients
- Normocytic normochromic anemia
- Urinalysis → microscopic hematuria, proteinuria
- Urine sediment → dysmorphic RBC and RBC casts → nephritic sediment
Chest x-ray/CT show multiple bilateral cavitating nodular lesions
Diagnosis should be confirmed by biopsy of affected tissue.
- Typically shows classic triad of:
1. Necrotic, partially granulomatous vasculitis of small and medium-sized vessels with adjacent palisading epithelioid histiocytes
2. Noncaseating, necrotizing granulomas (intravascular and extravascular) mainly in lung and upper airways
3. Necrotizing glomerulonephritis
Immunoglobulin A Vasculitis (Henoch-Schonlein Purpura, Anaphylactoid Purpura) Etiology
The exact pathogenesis is unknown and assumed to be multifactorial. Factors that likely play a role include:
- Preceding infection
- Up to 90% of cases preceded by viral or bacterial infection 1–3 weeks prior
- Most commonly an upper respiratory tract infection caused by group A Streptococcus
- GI infections also possible
- Many other organisms have also been associated with IgAV - IgA nephropathy
- Genetic predisposition
- Drugs (e.g., some antibiotics and antiarrhythmics) and vaccines (e.g., yellow fever, cholera)
Immunoglobulin A Vasculitis (Henoch-Schonlein Purpura, Anaphylactoid Purpura) Manifestations
- Skin → (∼ 100% of cases)
- Symmetrically distributed, raised, erythematous macules or urticarial lesions that coalesce into palpable purpura (dermal IgA deposition) (nonblanching skin lesions) (vasculitis within papillary dermis)
- Most common sites → the lower extremities, buttocks, and other areas of pressure or constraint (e.g., from socks or clothing) - Joints → (∼ 75% of cases) arthritis/arthralgia, most common in the ankles and knees (usually bilateral, self-limiting, and non-destructive. Children may present with limp)
- Gastrointestinal tract (∼ 60% of cases)
- Colicky abdominal pain (may be severe enough to mimic an acute abdomen)
- Can cause intussusception
- Bloody stools or melena
- Nausea/vomiting - Kidneys (∼ 50% of cases) → IgAV nephritis with signs and symptoms of nephritic syndrome (IgAV nephritis is very similar in pathogenesis and presentation to IgA nephropathy)
- Other organs
- Scrotum (scrotal swelling, pain, and tenderness)
- Central and peripheral nervous system (e.g., headaches, seizures, focal neurologic deficits, ataxia, intracerebral hemorrhage, central and peripheral neuropathy)
- Respiratory tract (e.g., mild interstitial changes, pulmonary hemorrhage)
- In rare cases → eyes (e.g., keratitis, uveitis)
Characterized by a tetrad of clinical features → palpable purpura, arthritis/arthralgia, GI symptoms, and renal disease. IgAV is one of the important differential diagnoses to consider in cases of pediatric limp.
Immunoglobulin A Vasculitis (Henoch-Schonlein Purpura, Anaphylactoid Purpura) Findings
Laboratory tests
- ↑ Platelet count (thrombocytopenia would indicate a condition other than IgAV)
- ↑ White blood cell count
- ↓ Hemoglobin (mild normochromic anemia may appear as a result of GI bleeding)
- Coagulation profile → usually normal
- ↑ IgA in serum
- Evidence of circulating IgA immune complexes
- ↓ Complement
- In case of preceding streptococcal infection → antistreptolysin O (ASO) titers
- ↑ Creatinine and/or BUN (indicates renal involvement)
- Electrolyte imbalances (due to GI manifestations and/or kidney involvement)
- Urinalysis to assess possible renal disease (hematuria, often with RBC casts, possibly proteinuria)
- ↑ ESR
- ↑ CRP
- In case of GI involvement → positive stool guaiac
Biopsy
- Indications → reserved for patients with unusual skin presentations or severe renal involvement (e.g., persistent nephritic syndrome)
1. Skin → leukocytoclastic vasculitis with IgA and C3 immune complex deposition (hallmark) in small vessels of the superficial dermis
2. Kidney - Mesangial IgA deposition
- C3 complement and fibrin
- Crescent formation in more severe cases (the extent of the crescent appearance is of prognostic importance)
IgAV is a unique cause of purpura without thrombocytopenia.
Immunoglobulin A Vasculitis (Henoch-Schonlein Purpura, Anaphylactoid Purpura) Complications
Renal
- In some cases, IgAV nephritis may progress to nephrotic syndrome
- Serious complication → rapid-progressive glomerulonephritis (RPGN) with crescent formation
Gastrointestinal
- Small bowel infarction or perforation
- Intussusception (intussusception as a complication of IgAV is classically ileoileal)
Microscopic Polyangiitis Manifestations
- Renal (∼ 90%) → pauci-immune glomerulonephritis with hypertension (has a poor prognosis)
- Lungs (∼ 50%) → pulmonary vasculitis with hemoptysis
- Skin (∼ 40%) → palpable purpura, nodules, necrosis
The nasopharynx is usually not affected.
Microscopic Polyangiitis Findings
Biopsy of involved organ
- Fibrinoid necrosis with infiltration of neutrophils
- No granulomas
Laboratory findings → MPO-ANCA/pANCA in ∼ 70% of cases
Cryoglobulinemic Vasculitis Etiology
- Viral infection
- 70–90% association with hepatitis C infection
- Formation of hepatitis C IgG and IgM rheumatoid factor → immune complex formation with hepatitis C antigen → complement activation and inflammation of blood vessels - Other underlying diseases → multiple myeloma, lymphoproliferative disorders, connective tissue diseases, autoimmune diseases (SLE), proliferative glomerulonephritis
Cryoglobulinemic Vasculitis Presentation
- Nonspecific systemic symptoms → fatigue, malaise, myalgia, arthralgia
- Skin lesions (nearly 100% of cases) → palpable purpura, ulceration, necrosis
- Vasomotor symptoms → Raynaud phenomenon, acrocyanosis
- Polyneuropathy
- Hepatosplenomegaly
- Glomerulonephritis (severe cases or late complication)
The triad of arthralgia, palpable purpura, and fatigue is seen in ∼ 30% of patients with mixed cryoglobulinemia.
Cryoglobulinemic Vasculitis Findings
Laboratory findings
- Cryoglobulinemia → cold-precipitable immunoglobulins or immune complexes (slow precipitation after72 hours)
- ↑ Rheumatoid factor (in almost all cases)
- Hypocomplementemia (90% of cases)
- Hepatitis C diagnostics (Hepatitis C RNA and anti-hepatitis C antibodies, ↑ Liver transaminases)
Skin or renal biopsy
- Inflammatory vascular changes and renal damage
- Cryoglobulin deposits (IgG and IgM complexes) may be detected in glomeruli.
Hereditary Hemorrhagic Telangiectasia
- Hereditary, systemic vasculopathy characterized by telangiectasia on the skin and mucosa, particularly in the area of the face (nose, lips, tongue)
- Pattern of inheritance → autosomal dominant
- Mutations in genes which code for TGF-β receptors (e.g., endoglin or ALK-1) → structural defects in the vessel wall → postcapillary venous pooling → formation of small and large arteriovenous shunts
Clinical features
- Recurrent epistaxis
- Telangiectasia involving the skin and mucous membranes (including GI tract)
- Cyanosis
Diagnosis
- Diagnostic criteria for HHT (Curaçao criteria)
1. Epistaxis
2. Teleangiectasias
3. Family history of HHT (at least one first-degree relative)
4. Signs of visceral involvement (e.g., pulmonary, gastrointestinal, cerebral) - Genetic testing
Management
- Skin telangiectasia can be treated by laser therapy or by injection of sclerosing agents.
- Embolization is used to treat large pulmonary and hepatic AV fistulas.
Complications
- High-output cardiac failure
- Paradoxical emboli → brain abscess and/or stroke (since the normal filtering function of the lungs is bypassed by large AV shunts in the lung)
- Chronic GI bleeding and/or hematuria → anemia
