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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Aortic Regurgitation Resident Survival Guide Microchapters
Overview
Causes
FIRE
Diagnosis
Acute
Chronic
Treatment
Acute
Chronic
Type of Valve and Anticoagulation
Do's
Don'ts

Overview

Aortic regurgitation (AR) refers to the retrograde or backward flow of blood from the aorta into the left ventricle during diastole.[1][2][3][4] The presentation depends on the response and adaptability of the left ventricle to the increased diastolic volume, in chronic AR the left ventricle has adapted by dilatation of its walls. However, in acute AR, a rapid increase in the diastolic volume is not tolerated by a normal size ventricle and this could lead to cardiogenic shock. The most common causes of acute aortic regurgitation are aortic dissection and infective endocarditis and the preferred treatment in both cases surgical intervention. The most common cause of chronic AR is bicuspid aortic valve and the treatment will depend on the stage of the disease. Acute AR is a life-threatening condition and must be recognized and treated promptly.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Click here for the complete list of causes.

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention. The algorithm below is based on the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease.[6][7]

Boxes in salmon color signify that an urgent management is needed.

Abbreviations: ECG: electrocardiogram; TTE: transthoracic echocardiography; TEE: transesophageal echocardiography; S1: first heart sound; P2: second heart sound, pulmonary component; S3: third heart sound

 
 
 
 
 
 
Identify cardinal findings that increase the pretest probability of aortic regurgitation

Acute aortic regurgitation
❑ Low pitched early diastolic murmur
❑ Best heard at the right 2nd intercostal space

❑ Decreased or absent S1
❑ Increased P2
❑ Sudden onset of dyspnea



Chronic aortic regurgitation
❑ High pitched holodiastolic decrescendo murmur

❑ Best heard at the upper left sternal border
❑ Increases with sitting forward, expiration and handgrip
Wide pulse pressure (≥ 60 mmHg)
S3
Corrigan's pulse: a rapid upstroke and collapse of the carotid artery pulse
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have any of the following findings that require urgent management?
Tachycardia
Hypotension
Altered mental status
Tachypnea
Oliguria
Cold extremities
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate resuscitation measures:
❑ Secure airway
❑ Administer oxygen
❑ 2 wide bore IV access
❑ ECG monitor
❑ Monitor vitals continuously
❑ ICU admission

Initiate medical therapy
❑ Administer nitroprusside 0.3-0.5 υg/kg/min IV (max 10 υg/kg/min), AND
❑ Administer dobutamine 0.5 υg/kg/min IV (max 20 υg/kg/min)

❑ Administer beta blockers in high suspicion of aortic dissection
Do not use them for other causes as they will block the compensatory tachycardia

Order urgent TTE
❑ Confirm aortic regurgitation
❑ Additional findings according to etiology:

Vegetations on the leaflets
❑ Aortic root dissection
In high suspicion of aortic dissection or when TTE is nondiagnostic, perform a TEE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the etiology based on clinical findings and echo?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Diagnostic clues:
Chest pain of the following characteristics:
❑ Sudden onset
❑ Intense
❑ Tearing and sharp
❑ Worsened by deep breathing or cough
❑ Relieved by sitting upright

Syncope
❑ Low pitched early diastolic murmur

❑ Best heard at the right 2nd intercostal space

❑ Aortic root dissection found on TTE
❑ Previous history of:

Marfan syndrome
Connective tissue disorder
 
 
 


Diagnostic clues:
❑ Persistent fever
❑ New valvular regurgitation murmur
❑ Previous blood culture positive
Vegetations found on TTE
❑ High risk factors:
❑ Pre-existing cardiac abnormality
Prosthetic valve
❑ Recent surgical or medical procedures
Intravenous drug use
❑ Recent bacterial infection
❑ History of previous endocarditis


❑ Evaluate the modified Duke criteria (click here to see the modified Duke criteria )

❑ Order blood cultures (if they have not been previously ordered)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immediate surgical intervention
 
 
 
Immediate surgical intervention
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Diagnosis

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.[6][7]

Abbreviations: BP: blood pressure; CXR: chest X-ray; ECG: electrocardiogram; LV: left ventricle; MI: myocardial infarction; TTE: transthoracic echocardiography; TEE: transesophageal echocardiography; TAVR: transcatheter aortic valve replacement; S1: first heart sound; S2: second heart sound; S3: third heart sound;

Acute Aortic Regurgitation

 
 
 
 
Characterize the symptoms:

❑ Sudden and severe dyspnea
Palpitations
Altered mental status
❑ Cold extremities
Oliguria

Symptoms suggestive of aortic dissection
Chest pain

❑ Sudden onset
❑ Intense
❑ Tearing and sharp
❑ Interscapular
❑ Worsened by deep breathing or cough
❑ Relieved by sitting upright

Syncope

Symptoms suggestive of infective endocarditis
Fever
Sweats
Fatigue
Pleuritic chest pain

Back pain
Weakness
Myalgias
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inquire about past medical history:
Cardiac disease:
Hypertension
Bicuspid aortic valve

Rheumatic fever
Marfan syndrome
Connective tissue disorder
Prosthetic valves
Intravenous drug use

❑ Substances used in the mixture
❑ Sharing the equipment
❑ The process of cleaning the equipment
❑ Previous infective endocarditis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:

Vitals
Temperature

Fever (suggestive of infective endocarditis)

Heart rate

Tachycardia

Blood pressure

❑ Systolic BP differential > 20 mmHg
Hypertension (suggestive of aortic dissection)
Hypotension (suggestive of severe regurgitation)

Respiratory rate

Tachypnea

Cardiovascular examination
Pulses

❑ Weak

Jugular venous distension
Cardiac auscultation

Murmur
❑ Low pitched early diastolic murmur (may be absent)
❑ Best heard at the right 2nd intercostal space in aortic dissection
Heart sounds
❑ Decreased or absent S1
❑ Increased P2 (suggestive of pulmonary hypertension)
S3 and S4 may be present

❑ Apical diastolic rumble Respiratory examination
Rales (suggestive of pulmonary congestion)

Wheeze
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order labs and tests:

TTE (most important test) (Class I; Level of Evidence: B)

In high suspicion of aortic dissection, perform a TEE

Chest X-ray

❑ Increase cardiac silhouette (suggestive of aortic dissection)
Widened mediastinum (suggestive of aortic root dilation)
❑ Pulmonary congestion (suggestive of pulmonary edema or pulmonary hypertension)

ECG

❑ Nonspecific changes of ST and T wave (due to LV enlargement)
Right coronary artery ischemic changes (suggestive of aortic dissection)
ST elevation in II, III, aVF (Inferior MI)
ST elevation in V3R and V4R (Right ventricle MI)
ST depression in V1-V3 (Posterior MI)

Blood culture (if suspected infective endocarditis)

Cardiac enzymes (Troponin, CK-MB)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine the etiology of the acute aortic regurgitation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



Diagnostic clues:
Chest pain of the following characteristics:
❑ Sudden onset
❑ Intense
❑ Tearing and sharp
❑ Worsened by deep breathing or cough
❑ Relieved by sitting upright

Syncope
❑ Low pitched early diastolic murmur

❑ Best heard at the right 2nd intercostal space

❑ Previous history of:

Marfan syndrome
Connective tissue disorder
 



Diagnostic clues:
❑ Persistent fever
❑ New valvular regurgitation murmur
❑ Positive blood culture
❑ Vegetations found on TTE
❑ High risk factors:
❑ Pre-existing cardiac abnormality
Prosthetic valve
❑ Recent surgical or medical procedures
Intravenous drug use
❑ Recent bacterial infection
❑ History of previous endocarditis
❑ Evaluate the modified Duke criteria (click here to see)


 
Other causes




 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Chronic Aortic Regurgitation

 
 
 
 
 
 
Characterize the symptoms:
❑ Asymptomatic
Dyspnea on exertion
Orthopnea
Paroxysmal nocturnal dyspnea
Palpitations
Chest pain
Shortness of breath
Cough
Altered mental status
Syncope
Fatigue
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:

Vitals
Heart rate:

Tachycardia (suggestive of reduced stroke volume)

Blood pressure:

Wide pulse pressure (≥ 60 mmHg)

Cardiovascular examination
❑ Pulses

Corrigan's pulse: a rapid upstroke and collapse of the carotid artery pulse

Cardiac auscultation

Murmur
❑ High pitched holodiastolic decrescendo murmur
❑ Best heard at the upper left sternal border
❑ Murmur increases with sitting forward, expiration and handgrip
Austin Flint murmur: a soft mid-diastolic rumble, best heard at the cardiac apex (suggestive of severe regurgitation)
Heart sounds
S2: decreased or absent A2; normal P2
S3 may be present (suggestive of left ventricular dysfunction)
S4 may also be present

❑ Search for other characteristic signs suggestive of aortic regurgitation

Traube's sign: 'pistol shot' pulse heard over the femoral artery
Müller's sign: systolic pulsations of uvula [8]
de Musset's sign: head bobbing with each heart beat
Hill's sign: ≥ 20 mmHg difference in popliteal and brachial systolic cuff pressures (suggestive of chronic severe AR)
Quincke's sign: pulsation of the capillary bed in the nail

Respiratory examination

Rales (seen when congestive heart failure has developed)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order imaging studies:

TTE (most important evaluation test) (Class I; Level of Evidence: B)
Chest X-ray

❑ Increase cardiac silhouette (suggestive of aortic dissection)
Widened mediastinum (suggestive of aortic root dilation)
Pulmonary congestion (suggestive of HF)

ECG

❑ Nonspecific changes of ST and T wave (due to LV enlargement)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Classify aortic regurgitation based on the following findings on TTE:
Vena contracta
❑ Jet/LVOT
❑ Regurgitant volume
❑ Regurgitant fraction
❑ Effective regurgitant orifice
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Risk of AI (Stage A)

❑ No regurgitation
 
Mild (Stage B)

Vena contracta <0.3 cm
❑ Jet/LVOT <25%
❑ Regurgitant volume <30 mL/beat
❑ Regurgitant fraction <30%
❑ Effective regurgitant orifice <0.10 cm²
 
Moderate (Stage B)

Vena contracta 0.3-0.6 cm
❑ Jet/LVOT 25-64%
❑ Regurgitant volume 30-59 mL/beat
❑ Regurgitant fraction 30-49%
❑ Effective regurgitant orifice 0.10-0.29 cm²
 
Severe

Vena contracta >0.6 cm
❑ Jet/LVOT ≥ 65%
❑ Regurgitant volume ≥60 mL/beat
❑ Regurgitant fraction ≥50%
❑ Effective regurgitant orifice ≥ 0.30 cm²
❑ Holodiastolic flow reversal in the proximal abdominal aorta
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asymptomatic

Stage C1
❑ Normal LVEF
❑ Mild to moderate dilatation
Stage C2
LV systolic dysfunction
❑ Decreased LVEF or severe LV dilatation
 
Symptomatic (Stage D)

❑ Normal or decreased LV systolic function
❑ Moderate to severe LV dilatation
 
 
 
 
 

Treatment

Treatment of Acute Aortic Regurgitation

Shown below is an algorithm for the treatment of acute aortic regurgitation according to the 2014 AHA/ACC Guidelines for the Management of Valvular Heart Disease[6][9] and the 2010 ACCF/AHA Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease[10]


 
 
 
 
 
 
 
 
Determine the etiology and the grade of regurgitation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild or moderate regurgitation
(Stage B)
 
Severe regurgitation
(Stage C or D)
 
Mild or moderate regurgitation
(Stage B)
 
Severe regurgitation
(Stage C or D)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient has any of the following?
❑ S.aureus infection
❑ Fungal infection
❑ Large vegetation
 
 
 
 
 
 
Replacement of supra-coronary ascending aorta
 
Aortic root replacement, OR
Valve-sparing aortic root replacement
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate antibiotic treatment
Click here for a complete list of pathogen specific antibiotics regimens
 
 
Schedule for AVR (Class I; Level of Evidence: B)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If the patient does not get better after 5-7 days:
Schedule for AVR (Class I; Level of Evidence: B)
 
 
 
 
 
 
 
 
 
 


Treatment of Chronic Aortic Regurgitation

Shown below is an algorithm summarizing the treatment approach to chronic aortic regurgitation according to the 2014 AHA/ACC Guidelines on the Management of Valvular Heart Disease.[6][7]

Abbreviations: TTE: transthoracic echocardiography; AVR: aortic valve replacement; CCB: calcium channel blocker; ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker

 
 
 
 
What is the stage of aortic regurgitation according to the TTE?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No regurgitation
(Stage A)
 
Progressive regurgitation (Stage B)
Mild
❑ Vena contracta <0.3 cm
❑ Jet/LVOT <25%
❑ Regurgitant volume <30 mL/beat
❑ Regurgitant fraction <30%
❑ Effective regurgitant orifice <0.10 cm²
Moderate
❑ Vena contracta 0.3-0.6 cm
❑ Jet/LVOT 25-64%
❑ Regurgitant volume 30-59 mL/beat
❑ Regurgitant fraction 30-49%
❑ Effective regurgitant orifice 0.10-0.29 cm²
 
 
 
 
 
Severe regurgitation

❑ Vena contracta >0.6 cm
❑ Jet/LVOT ≥ 65%
❑ Regurgitant volume ≥60 mL/beat
❑ Regurgitant fraction ≥50%
❑ Effective regurgitant orifice ≥ 0.30 cm²
❑ Holodiastolic flow reversal in the proximal abdominal aorta
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the patient symptomatic?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asymptomatic patients
❑ Normal valve
Bicuspid valve
Sclerotic valve
 
Asymptomatic patients
❑ Control hypertension preferably with
❑ Dihydropyridine CCB, or
ACE inhibitors/ARBs

(Class I; Level of Evidence: B)

 
 
 
NO
(Stage C)
 
 
 
YES
(Stage D)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ No treatment is needed
 
Perform a periodic echo (Class I; Level of Evidence:B)
❑ Every 3 -5 years for mild regurgitation
❑ Every 1 - 2 years for moderate regurgitation
 

❑ Normal LVEF
❑ Mild to moderate dilatation
 
 

LV systolic dysfunction, and
❑ Decreased LVEF, or
❑ Severe LV dilatation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If patient undergoes another cardiac surgery:
Schedule for AVR (Class IIa; Level of Evidence: C)
 
Perform a periodic echocardiogram every 6 - 12 months (Class I; Level of Evidence: B)
❑ Perform an exercise stress test
 
 
 
 
Schedule for AVR (Class I; Level of Evidence: B)
❑ Initiate medical therapy with ACE inhibitors/ARBs or beta blockers if patient has contraindications for surgery
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient developed symptoms in the stress test?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Initiate medical therapy with vasodilators
Nifedipine 30-60 mg/day
Hydralazine 10-25 mg/ q8hrs
 
❑ No treatment is needed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If the patient undergoes another cardiac surgery:
Schedule for AVR (Class IIa; Level of Evidence: C)
 
 
 
 
 
 
 
 
 
 

Type of Valve and Discharge Anticoagulation Therapy

Abbreviations: AVR: Aortic valve replacement; INR: International normalized ratio; TAVR Tansthoracic aortic valve replacement

 
 
 
 
 
 
Determine:
Age
Contraindications for anticoagulation
❑ Major bleeding diathesis or coagulopathy
❑ Uncontrolled severe hypertension (systolic blood pressure >200 mmHg)
❑ Recent head trauma
❑ Platelet count < 100 000
Pregnancy
❑ Hypersensitivity to warfarin
Hemorrhagic stroke
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Patients ≤ 60 years old (Class IIa; Level of Evidence: B), AND
❑ No contraindication for anticoagulation
 
❑ Patients 60 - 70 years old
❑ No contraindication for anticoagulation
 
❑ Patients ≥ 70 years old (Class IIa; Level of Evidence: B), OR
❑ Patients with contraindications for anticoagulation therapy (Class I; Level of Evidence: C)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mechanical Prosthesis
Avoid the use of direct thrombin inhibitors or anti-Xa agents in patients with mechanical prosthesis (Class III; Level of Evidence: B)
 
Either a bioprosthesic or mechanical valve is reasonable (Class IIa; Level of Evidence: B).
 
Bioprosthesis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient with risk factors†
 
Patient without risk factors†
 
Surgical AVR
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer for long term:
Warfarin to achieve INR of 3.0
Aspirin 75-100 mg/d
 
Administer for long term:
Warfarin to achieve INR of 2.5
Aspirin 75-100 mg/d
 
❑ Administer warfarin to achieve INR of 2.5 for 3 months
❑ Then administer aspirin 75-100 mg/d long term
 
Administer for 6 months:
Clopidogrel 75 mg/d
Aspirin 75-100 mg/d
 


†Risk factors for thromboembolism include atrial fibrillation, hypercoagulable conditions, left ventricle dysfunction, and previous thromboembolism.

Do's

❑ Perform a cardiac MRI in patients with moderate or severe AR with an inconclusive TTE to assess LV systolic function, systolic and diastolic volumes, and measurement of AR severity. (Class I; Level of Evidence: B)
❑ Exercise stress test could be useful to assess symptomatic status and functional capacity of patents with severe aortic regurgitation
❑ ❑

Don'ts

❑ Do not use beta blockers in aortic regurgitation that is not caused by aortic dissection as it will block the compensatory tachycardia.
❑ Do not use intra-aortic baloon counterpulsation in severe acute AI as it will increase the aortic diastolic pressure and the regurgitant volume.
❑ Do not give antibiotics to patients with known VHD before blood cultures are obtained for unexplained fever. (Class III; Level of Evidence: C)
❑ Do not give ACE inhibitors to pregnant patients with aortic regurgitation. (Class III; Level of Evidence: B)






References

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  2. Weissman NJ (2001). "Appetite suppressants and valvular heart disease". Am. J. Med. Sci. 321 (4): 285–91. doi:10.1097/00000441-200104000-00008. PMID 11307869.
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  4. Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G (2007). "Valvular heart disease and the use of dopamine agonists for Parkinson's disease". N. Engl. J. Med. 356 (1): 39–46. doi:10.1056/NEJMoa054830. PMID 17202454.
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  6. 6.0 6.1 6.2 6.3 Nishimura, R. A.; Otto, C. M.; Bonow, R. O.; Carabello, B. A.; Erwin, J. P.; Guyton, R. A.; O'Gara, P. T.; Ruiz, C. E.; Skubas, N. J.; Sorajja, P.; Sundt, T. M.; Thomas, J. D. (2014). "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". Circulation. doi:10.1161/CIR.0000000000000031. ISSN 0009-7322.
  7. 7.0 7.1 7.2 Bonow, R. O.; Carabello, B. A.; Chatterjee, K.; de Leon, A. C.; Faxon, D. P.; Freed, M. D.; Gaasch, W. H.; Lytle, B. W.; Nishimura, R. A.; O'Gara, P. T.; O'Rourke, R. A.; Otto, C. M.; Shah, P. M.; Shanewise, J. S. (2008). "2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Circulation. 118 (15): e523–e661. doi:10.1161/CIRCULATIONAHA.108.190748. ISSN 0009-7322.
  8. Williams BR, Steinberg JP (2006). "Images in clinical medicine. Müller's sign". The New England Journal of Medicine. 355 (3): e3. doi:10.1056/NEJMicm050642. PMID 16855259. Retrieved 2012-04-15. Unknown parameter |month= ignored (help)
  9. Hamirani, Y. S.; Dietl, C. A.; Voyles, W.; Peralta, M.; Begay, D.; Raizada, V. (2012). "Acute Aortic Regurgitation". Circulation. 126 (9): 1121–1126. doi:10.1161/CIRCULATIONAHA.112.113993. ISSN 0009-7322.
  10. Hiratzka, L. F.; Bakris, G. L.; Beckman, J. A.; Bersin, R. M.; Carr, V. F.; Casey, D. E.; Eagle, K. A.; Hermann, L. K.; Isselbacher, E. M.; Kazerooni, E. A.; Kouchoukos, N. T.; Lytle, B. W.; Milewicz, D. M.; Reich, D. L.; Sen, S.; Shinn, J. A.; Svensson, L. G.; Williams, D. M. (2010). "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine". Circulation. 121 (13): e266–e369. doi:10.1161/CIR.0b013e3181d4739e. ISSN 0009-7322.


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