Third degree atrioventricular block

A 60-year-old male presents with fatigue, dizziness, lightheadedness, and presyncope over several days. He also reports chest pain and shortness of breath on exertion. On examination, the jugular venous pulse shows cannon a waves. Vital signs reveal severe bradycardia at 35/min with a regular pulse and a blood pressure of 110/70 mmHg. Electrocardiography demonstrates complete dissociation between P waves and QRS complexes, with constant P-P and R-R intervals. The P waves march through independently. The QRS complexes are wide, suggesting a ventricular escape rhythm. Diagnosis?

Diagnosis is Third-degree (complete) atrioventricular block.

1. Definition

Third-degree AV block is characterized by complete failure of atrial impulses to conduct to the ventricles, resulting in atrioventricular dissociation.

The atria and ventricles therefore depolarize independently, with the atria usually controlled by the SA node and the ventricles maintained by a junctional or ventricular escape rhythm.

2. Etiology

1. Degenerative fibrosis and sclerosis of the cardiac conduction system
• A common cause of acquired chronic AV block in older adults
2. Ischemic heart disease
• Acute myocardial infarction
• Chronic ischemic conduction system disease
3. Drugs that impair AV conduction
• Beta blockers
• Non-dihydropyridine calcium channel blockers
• Digoxin
• Amiodarone
4. Electrolyte and metabolic abnormalities
• Hyperkalemia
5. Inflammatory or infectious cardiac disease
• Myocarditis
• Lyme carditis
6. Infiltrative or systemic cardiac disease
• Cardiac sarcoidosis
• Amyloidosis
• Hemochromatosis
7. Iatrogenic or postprocedural conduction system injury
• Cardiac surgery
• Transcatheter or catheter-based cardiac procedures
8. Congenital complete AV block

3. Pathophysiology

1. There is complete interruption of conduction from the atria to the ventricles.
2. The atria continue to depolarize independently, usually under SA node control.
3. Ventricular activation is maintained by an escape pacemaker.
• Junctional escape rhythm
• Usually narrow QRS complexes
• Typically faster and more reliable
• Usually approximately 35 to 50/min
• Ventricular escape rhythm
• Usually wide QRS complexes
• Typically slower and less reliable
• Usually approximately 20 to 40/min
4. A more distal ventricular escape focus generally produces a slower and less reliable escape rhythm.
5. Severe bradycardia reduces cardiac output, which may cause cerebral hypoperfusion, myocardial ischemia, heart failure, presyncope, or syncope.

4. Clinical Features

4.1 Core Features

1. Severe bradycardia
2. AV dissociation
3. Cannon a waves

Cannon a waves occur when the atria intermittently contract against a closed tricuspid valve because atrial and ventricular contractions are dissociated.

4.2 Additional Features

1. Fatigue
2. Dizziness or lightheadedness
3. Presyncope or syncope
4. Exercise intolerance
5. Chest pain
6. Dyspnea
7. Heart failure in severe cases

5. Diagnosis

5.1 Electrocardiography

Typical ECG findings include:

1. No fixed relationship between P waves and QRS complexes
2. P waves march through independently
3. Atrial and ventricular rhythms are independent
4. P-P intervals are usually regular
5. R-R intervals of the escape rhythm are usually regular
6. The atrial rate is greater than the ventricular rate
7. The PR interval varies because there is no consistent relationship between atrial and ventricular depolarization

The QRS morphology depends mainly on the escape focus:

• Narrow QRS usually suggests a junctional escape focus
• Wide QRS usually suggests a distal ventricular escape focus

A wide QRS supports a distal escape mechanism but does not by itself definitively localize the site of AV block, because pre-existing bundle branch or intraventricular conduction disease can also widen the QRS complex.

In this patient, the ventricular rate of approximately 35/min with wide QRS complexes strongly suggests a ventricular escape rhythm.

5.2 Additional Evaluation

Evaluation should identify reversible or treatable causes and associated cardiac disease.

1. 12-lead ECG
2. Serum electrolytes, particularly potassium
3. Cardiac biomarkers when myocardial ischemia or infarction is suspected
4. Medication review for drugs that impair AV conduction
5. Evaluation for myocardial ischemia or infarction
6. Echocardiography when structural heart disease is suspected
7. Additional testing for specific causes such as Lyme carditis, myocarditis, or infiltrative disease when clinically indicated

6. Management

6.1 Initial Assessment

Assess whether the bradycardia is producing cardiopulmonary compromise, including:

1. Hypotension
2. Acutely altered mental status
3. Signs of shock
4. Ischemic chest discomfort
5. Acute heart failure

At the same time, identify and treat potentially reversible causes.

6.2 Acute Management

For persistent symptomatic bradycardia with cardiopulmonary compromise:

1. Atropine
• May be administered according to the adult bradycardia algorithm
• It is less likely to be effective when the block is located in the His-Purkinje system
2. If atropine is ineffective:
• Transcutaneous pacing
• Dopamine infusion
• Epinephrine infusion
3. Temporary transvenous pacing
• If hemodynamically unstable bradycardia persists despite medical therapy, temporary transvenous pacing is reasonable
• It may be particularly important when the escape rhythm is slow, unstable, or unreliable

6.3 Definitive Management

Permanent pacemaker implantation is recommended in patients with acquired third-degree AV block that is not caused by a reversible or physiologic condition, regardless of the presence or absence of symptoms.

6.4 Additional Measures

1. Treat reversible causes
2. Discontinue or adjust offending medications when appropriate
3. Correct electrolyte abnormalities
4. Treat myocardial ischemia or infarction when present
5. Treat specific infectious, inflammatory, or infiltrative diseases when identified

7. Key Clinical Insight

Severe bradycardia + cannon a waves + complete AV dissociation on ECG strongly indicates third-degree AV block.

In this patient, the independent P waves and QRS complexes, regular atrial and ventricular rhythms, severe bradycardia, and wide QRS escape complexes establish the diagnosis of third-degree AV block with a likely ventricular escape rhythm.

References

1. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay. Circulation. 2019;140(8):e382-e482. doi:10.1161/CIR.0000000000000628.
2. Wigginton JG, Agarwal S, Bartos JA, et al. Part 9: Advanced Life Support: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2025;152(Suppl 2):S538-S577. doi:10.1161/CIR.0000000000001376.
3. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. European Heart Journal. 2021;42(35):3427-3520. doi:10.1093/eurheartj/ehab364.

Cardiac Tamponade

A 38-year-old male with kidney failure receiving maintenance dialysis presents with progressive shortness of breath, chest discomfort, and fatigue over several days. Vital signs reveal hypotension at 90/60 mmHg, tachycardia at 120/min, and an oxygen saturation of 92% on room air. Peripheral pulses become weaker during inspiration, consistent with pulsus paradoxus. On examination, there is jugular venous distension and muffled heart sounds. Electrocardiography demonstrates low-voltage QRS complexes and electrical alternans. Echocardiography shows a pericardial effusion with right ventricular diastolic collapse. Diagnosis?

Diagnosis is Cardiac tamponade.

1. Definition

Cardiac tamponade is a life-threatening hemodynamic syndrome caused by accumulation of fluid, blood, pus, or other material within the pericardial space, resulting in increased intrapericardial pressure, impaired cardiac filling, reduced stroke volume, and decreased cardiac output.

When severe, cardiac tamponade produces obstructive shock.

2. Etiology

1.       Kidney failure-related pericardial disease

o    Uremic pericarditis

o    Dialysis-associated pericarditis

Uremic pericarditis generally refers to pericarditis occurring before dialysis or within approximately 8 weeks after dialysis initiation. Pericarditis developing after at least 8 weeks of maintenance dialysis is commonly termed dialysis-associated pericarditis.

2.       Malignancy

o    Lung cancer

o    Breast cancer

o    Lymphoma

o    Other metastatic malignancies

3.       Trauma

o    Penetrating cardiac trauma

o    Blunt thoracic trauma

4.       Infectious or inflammatory pericardial disease

o    Viral or idiopathic pericarditis

o    Tuberculosis

o    Purulent bacterial pericarditis

o    Systemic inflammatory or autoimmune disease

o    Post-cardiac injury syndrome

5.       Acute myocardial infarction with mechanical complication

o    Ventricular free-wall rupture

6.       Iatrogenic causes

o    Cardiac catheterization

o    Electrophysiologic procedures

o    Device implantation

o    Cardiac surgery

o    Other invasive cardiovascular procedures

7.       Acute aortic syndromes

o    Aortic dissection or rupture with hemopericardium

3. Pathophysiology

1.       Pericardial fluid accumulates, causing an increase in intrapericardial pressure.

2.       When intrapericardial pressure becomes sufficiently high, it impairs diastolic filling of the cardiac chambers.

3.       Right-sided chambers are particularly susceptible because of their relatively lower intracavitary pressures.

4.       Impaired ventricular filling leads to:

o    Reduced preload

o    Reduced stroke volume

o    Reduced cardiac output

5.       Compensatory mechanisms include:

o    Tachycardia

o    Increased systemic vascular resistance

6.       Progressive hemodynamic compromise can result in:

o    Hypotension

o    Obstructive shock

o    Cardiac arrest

The clinical severity depends not only on the total volume of pericardial fluid but also on the rate of fluid accumulation, pericardial compliance, and intracardiac filling pressures.

Rapid accumulation of a relatively small volume may therefore cause tamponade, whereas a slowly accumulating effusion may become much larger before producing hemodynamic compromise.

4. Clinical Features

4.1 Beck Triad

The classic Beck triad consists of:

1.       Hypotension

2.       Jugular venous distension

3.       Muffled heart sounds

The complete triad is not present in every patient, particularly in subacute or nontraumatic tamponade.

4.2 Additional Features

1.       Tachycardia

2.       Dyspnea

3.       Tachypnea

4.       Chest discomfort

5.       Fatigue

6.       Weak peripheral pulses

7.       Cool extremities in advanced circulatory compromise

8.       Narrow pulse pressure

9.       Elevated jugular venous pressure

10.    Pulsus paradoxus

4.3 Pulsus Paradoxus

Pulsus paradoxus is an exaggerated inspiratory decrease in systolic blood pressure of greater than 10 mmHg.

During inspiration, increased right ventricular filling within a pressure-constrained pericardial space shifts the interventricular septum toward the left ventricle, reducing left ventricular filling and systemic stroke volume.

Clinically, this may be appreciated as weakening of the peripheral pulse during inspiration.

5. Diagnosis

Cardiac tamponade is a clinical and hemodynamic diagnosis supported by echocardiographic findings.

5.1 Electrocardiography

ECG findings may include:

1.       Sinus tachycardia

2.       Low-voltage QRS complexes

3.       Electrical alternans

Electrical alternans refers to beat-to-beat variation in the amplitude or axis of the QRS complexes and may occur when the heart swings within a large pericardial effusion.

Neither low voltage nor electrical alternans is required for the diagnosis.

5.2 Chest X-Ray

Chest radiography may demonstrate:

1.       Enlarged cardiac silhouette when a large pericardial effusion has accumulated gradually

A normal cardiac silhouette does not exclude acute cardiac tamponade, particularly when fluid accumulates rapidly.

5.3 Echocardiography

Transthoracic echocardiography is the key initial imaging modality for suspected cardiac tamponade because it identifies the effusion and assesses its hemodynamic consequences.

Important findings include:

1.       Pericardial effusion

2.       Right atrial collapse or inversion, particularly when it persists for more than one-third of the cardiac cycle

3.       Right ventricular early diastolic collapse

4.       Exaggerated respiratory variation in transvalvular Doppler flow

5.       Plethoric inferior vena cava with reduced inspiratory collapse

6.       Exaggerated ventricular interdependence

7.       A swinging heart in a large effusion

Right atrial collapse or inversion may occur relatively early in the evolution of tamponade, particularly when it persists for a substantial portion of the cardiac cycle.

Brief isolated right atrial collapse is less specific and should not be interpreted in isolation.

Right ventricular collapse during early diastole is an important and more specific echocardiographic sign of hemodynamically significant tamponade.

No single echocardiographic sign should be interpreted in isolation. Echocardiographic findings must be integrated with the patient's clinical and hemodynamic status.

In this patient, hypotension, jugular venous distension, pulsus paradoxus, pericardial effusion, and right ventricular diastolic collapse strongly support cardiac tamponade.

5.4 Hemodynamic Findings

When invasive hemodynamic assessment is performed, findings may include:

1.       Elevation and approximate equalization of intracardiac diastolic pressures

2.       Elevated right atrial pressure

3.       Attenuated or absent y descent in the right atrial pressure waveform

4.       Reduced cardiac output

Cardiac catheterization is not routinely required for diagnosis when the clinical and echocardiographic findings are diagnostic.

6. Management

6.1 Initial Management

Cardiac tamponade with hemodynamic compromise is a medical emergency.

Initial measures include:

1.       Continuous hemodynamic monitoring

2.       Supplemental oxygen when clinically indicated

3.       Establishment of intravenous access

4.       Identification and treatment of the underlying cause

5.       Immediate preparation for pericardial drainage

6.2 Definitive Management

The definitive treatment is drainage of the pericardial fluid.

For an unstable patient:

1.       Urgent image-guided pericardiocentesis

o    Echocardiographic or fluoroscopic guidance is preferred

2.       Surgical pericardial drainage may be required when:

o    Percutaneous drainage is not feasible

o    Purulent pericarditis is present

o    There is traumatic or active intrapericardial bleeding

o    Surgical correction of the underlying cause is required

6.3 Temporizing Measures

While definitive drainage is being arranged:

1.       Cautious intravenous fluid administration

o    May temporarily increase venous return and maintain cardiac filling

o    It should not delay definitive pericardial drainage

2.       Avoid unnecessary diuresis

o    Reduction in preload may worsen hemodynamic compromise

3.       Avoid positive-pressure ventilation when possible

o    Increased intrathoracic pressure can reduce venous return and precipitate further hemodynamic deterioration

If mechanical ventilation is unavoidable, it requires careful hemodynamic management.

6.4 Kidney Failure-Related Pericardial Disease

In patients with kidney failure, dialysis initiation or intensification is important when uremic or dialysis-associated pericarditis is suspected.

However, established cardiac tamponade requires urgent pericardial drainage, and dialysis should not be used as a substitute for immediate decompression in a hemodynamically compromised patient.

7. Key Clinical Insight

Hypotension + jugular venous distension + muffled heart sounds + pulsus paradoxus + pericardial effusion with right ventricular diastolic collapse strongly indicates cardiac tamponade.

In this patient, the combination of hypotension, tachycardia, jugular venous distension, muffled heart sounds, pulsus paradoxus, low-voltage QRS complexes, electrical alternans, and right ventricular diastolic collapse establishes a clinical picture of cardiac tamponade with hemodynamic compromise.

The history of kidney failure receiving maintenance dialysis raises concern for kidney failure-related pericardial disease, but whether this should specifically be classified as uremic or dialysis-associated pericarditis depends on the timing of symptom onset relative to dialysis initiation and the adequacy of dialysis.

References

1.       Schulz-Menger J, Collini V, Gröschel J, et al. 2025 ESC Guidelines for the management of myocarditis and pericarditis. European Heart Journal. 2025;46(40):3952-4041. doi:10.1093/eurheartj/ehaf192.

2.       Wang TKM, Klein AL, Cremer PC, et al. 2025 Concise Clinical Guidance: An ACC Expert Consensus Statement on the Diagnosis and Management of Pericarditis. Journal of the American College of Cardiology. 2025;86(25):2691-2719. doi:10.1016/j.jacc.2025.05.023.

3.       Rosen RJ, Valeri AM. Management of Patients with Kidney Failure and Pericarditis. Clinical Journal of the American Society of Nephrology. 2023;18(2):270-272. doi:10.2215/CJN.07470622.

Prinzmetal angina

A 20-year-old female presents with recurrent episodes of central chest pain that are non-exertional, sudden in onset, and last approximately 5 to 15 minutes. The pain is substernal and severe, radiates to the left arm, jaw, and neck, and is associated with nausea and diaphoresis. She has a history of Raynaud disease. Vital signs are normal between episodes. Electrocardiography during an ergonovine provocation test demonstrates transient ST-segment elevation. Coronary angiography demonstrates coronary vasospasm without significant obstructive atherosclerotic disease. Diagnosis?

Diagnosis is Prinzmetal (variant) angina, a classic form of vasospastic angina.

1. Definition

Prinzmetal angina, also called variant angina, is a classic form of vasospastic angina caused by transient constriction of an epicardial coronary artery, producing a dynamic reduction in coronary blood flow and transient myocardial ischemia.

Classic Prinzmetal angina is characterized by episodes of angina, usually occurring at rest, accompanied by transient ST-segment elevation.

Vasospastic angina may occur in patients with normal or near-normal coronary arteries, but the presence of coexisting coronary atherosclerosis does not exclude the diagnosis.

2. Etiology and Predisposing Factors

The underlying mechanism is abnormal coronary vasomotor reactivity. Important mechanisms and associated factors include:

1.       Hyperreactivity of coronary vascular smooth muscle

2.       Endothelial dysfunction

3.       Autonomic and vasomotor abnormalities

4.       Cigarette smoking

o    An important modifiable risk factor for coronary vasospasm

5.       Vasoconstrictive substances or drugs

o    Cocaine

o    Amphetamines and other sympathomimetics

o    Ergot derivatives

o    Other vasoconstrictive medications

6.       Potential precipitating factors

o    Cold exposure

o    Emotional stress

o    Hyperventilation

o    Alcohol in susceptible individuals

7.       Associated vasomotor disorders

o    Raynaud disease

o    Migraine

These associations may support a tendency toward abnormal vasomotor reactivity but are not diagnostic of vasospastic angina.

3. Pathophysiology

1.       A coronary artery undergoes transient intense vasoconstriction.

2.       The vasospasm causes a marked temporary reduction in the coronary arterial lumen.

3.       Coronary blood flow decreases, producing transient myocardial ischemia.

4.       Severe epicardial coronary spasm may produce transient myocardial ischemia with ST-segment elevation.

5.       When the vasospasm resolves spontaneously or after administration of a vasodilator such as a nitrate, coronary blood flow is restored and the ECG changes typically resolve.

6.       Prolonged or severe vasospasm can cause:

o    Myocardial infarction

o    Ventricular arrhythmias

o    Bradyarrhythmias

o    Sudden cardiac death

4. Clinical Features

4.1 Core Features

1.       Angina occurring predominantly at rest

2.       Sudden onset of chest pain

3.       Episodes often occur in a circadian pattern, particularly at night or in the early morning

4.       Exercise tolerance may be relatively preserved

5.       Episodes are usually brief but may recur in clusters

6.       Symptoms generally respond rapidly to short-acting nitrates

Although rest angina is characteristic, vasospastic angina is not absolutely restricted to rest and can occasionally occur during exertion.

4.2 Associated Features

During an episode, patients may experience:

1.       Diaphoresis

2.       Nausea

3.       Palpitations

4.       Presyncope or syncope if significant arrhythmia occurs

5.       Radiation of pain to the arm, shoulder, jaw, neck, or back

A history of a vasomotor disorder such as Raynaud disease may increase clinical suspicion but does not establish the diagnosis.

5. Diagnosis

The diagnosis is based on the characteristic clinical presentation together with documentation of transient myocardial ischemia or coronary artery spasm.

5.1 Electrocardiography

During an episode, the ECG may demonstrate:

1.       Transient ST-segment elevation

2.       Transient ST-segment depression

3.       Other transient ischemic changes

In classic Prinzmetal or variant angina, transient ST-segment elevation is characteristic.

The ECG may return completely to baseline after the vasospasm resolves.

5.2 Cardiac Biomarkers

1.       Cardiac biomarkers are often normal after brief episodes of reversible ischemia.

2.       Troponin may become elevated when vasospasm is prolonged or sufficiently severe to cause myocardial injury or infarction.

5.3 Coronary Angiography

Coronary angiography may show:

1.       No significant obstructive coronary artery disease

2.       Transient epicardial coronary vasospasm

3.       Resolution of the spasm after administration of an intracoronary nitrate

Vasospastic angina can also occur in patients with coexisting atherosclerotic coronary disease. Therefore, normal coronary arteries are not required for the diagnosis.

5.4 Provocation Testing

When spontaneous episodes have not been adequately documented, coronary vasospasm may be assessed during invasive coronary angiography using pharmacologic provocation.

Common provocative agents include:

1.       Acetylcholine

2.       Ergonovine

A positive test for epicardial coronary vasospasm typically requires:

1.       Reproduction of the patient's characteristic chest pain

2.       Ischemic ECG changes

3.       Severe transient epicardial coronary constriction

Severe epicardial coronary vasospasm is generally defined by approximately 90% or greater angiographic constriction together with characteristic symptoms and ischemic ECG changes.

Contemporary ESC criteria use at least 90% reduction in coronary lumen diameter, COVADIS criteria use greater than 90% constriction, and JCS criteria specify greater than 90% focal stenosis or 90% diffuse vasoconstriction involving at least two contiguous coronary segments.

Provocation testing should be performed in an appropriately equipped cardiac catheterization laboratory by experienced clinicians because significant bradyarrhythmias, ventricular arrhythmias, or prolonged vasospasm can occur.

In this patient, transient ST-segment elevation during provocation together with angiographically demonstrated coronary vasospasm strongly supports the diagnosis.

6. Management

6.1 Acute Treatment

Short-acting nitrates are used for rapid relief of an acute vasospastic episode.

Examples include:

1.       Sublingual nitroglycerin

2.       Sublingual or other rapidly acting nitrate preparations

Nitrates relax coronary vascular smooth muscle and usually relieve the vasospasm rapidly.

6.2 Long-Term Prevention

Calcium channel blockers are the first-line preventive treatment for vasospastic angina.

Examples include:

1.       Diltiazem

2.       Verapamil

3.       Amlodipine

4.       Nifedipine

In patients with severe or persistent vasospastic angina, higher doses or a combination of a dihydropyridine and non-dihydropyridine calcium channel blocker may be required under appropriate clinical supervision.

6.3 Nitrates for Prevention

Long-acting nitrates may be added when symptoms remain inadequately controlled with calcium channel blockers.

They are generally used as adjunctive therapy rather than as the sole first-line preventive treatment.

6.4 Risk Factor and Trigger Modification

Patients should be advised to:

1.       Stop smoking

2.       Avoid cocaine and other sympathomimetic recreational drugs

3.       Avoid medications or substances known to precipitate coronary vasospasm when possible

4.       Manage conventional cardiovascular risk factors when present

6.5 Beta Blockers

Beta blockers are generally avoided in isolated vasospastic angina, particularly agents without alpha-1 adrenergic blocking activity, because they may exacerbate coronary vasospasm in susceptible patients.

This is particularly relevant to nonselective beta blockers.

If a beta blocker is required for another compelling indication, treatment should be individualized rather than considering all beta blockers absolutely contraindicated.

7. Complications

Vasospastic angina can occasionally produce serious complications, particularly when vasospasm is prolonged or involves a major coronary artery.

Complications include:

1.       Ventricular tachycardia or ventricular fibrillation

2.       Bradyarrhythmias or atrioventricular block

3.       Syncope

4.       Myocardial infarction

5.       Sudden cardiac death

8. Key Clinical Insight

Rest angina + transient ST-segment elevation + angiographically demonstrated reversible coronary vasospasm strongly indicates Prinzmetal or variant angina.

In this patient, the combination of recurrent non-exertional chest pain, transient ST-segment elevation during pharmacologic provocation, and angiographically demonstrated coronary vasospasm without significant obstructive coronary disease establishes the diagnosis of Prinzmetal (variant) angina, a classic form of vasospastic angina.

Her history of Raynaud disease provides an additional clue to abnormal vasomotor reactivity but is not itself diagnostic.

References

1.       Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. European Heart Journal. 2024;45(36):3415-3537. doi:10.1093/eurheartj/ehae177.

2.       Hokimoto S, Kaikita K, Yasuda S, et al. JCS/CVIT/JCC 2023 Guideline Focused Update on Diagnosis and Treatment of Vasospastic Angina (Coronary Spastic Angina) and Coronary Microvascular Dysfunction. Circulation Journal. 2023;87(6):879-936. doi:10.1253/circj.CJ-22-0779.

3.       Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. European Heart Journal. 2017;38(33):2565-2568. doi:10.1093/eurheartj/ehv351.