Critical Arrhythmia Severity Assessment Explained

Did you know that arrhythmias affect millions of people worldwide? They can greatly impact their lives. We will look at the different levels of arrhythmia seriousness. Understanding their severity is key for managing them well.

Knowing how serious arrhythmias are is important for treatment. Healthcare experts use seriousness levels to tailor care. This helps those with arrhythmias get the right support.

How critical are they? Understand the arrhythmia severity assessment and when an irregular beat is considered dangerous.

Key Takeaways

• Arrhythmias can have a significant impact on a person’s quality of life.
• Understanding the severity of arrhythmias is vital for effective management.
• Assessing arrhythmia seriousness levels helps healthcare professionals provide personalized care.
• Arrhythmias can range from mild to life-threatening.
• Effective treatment depends on accurate assessment of arrhythmia severity.

Understanding Cardiac Arrhythmias

It’s important for both patients and doctors to understand how serious cardiac arrhythmias are. These irregular heartbeats can be mild or very dangerous. We’ll explore what arrhythmias are, how they differ from normal heartbeats, and how common they are.

Definition and Basic Mechanisms

Cardiac arrhythmias happen when the heart’s electrical system gets disrupted. This can be due to heart disease, imbalances in electrolytes, or certain medicines. The heart’s electrical system is complex, involving many pathways and feedback loops that can sometimes fail, causing arrhythmias.

Normally, the heart beats in a regular rhythm, thanks to its electrical system. But when this system is changed, arrhythmias can occur. The severity of these arrhythmias depends on several factors, including their type, frequency, and the presence of underlying heart disease.

Normal Heart Rhythm vs. Arrhythmias

A normal heart rhythm is steady, usually between 60 to 100 beats per minute when resting. Arrhythmias, on the other hand, can make the heart beat too fast, too slow, or irregularly. Understanding the difference between normal heart rhythm and arrhythmias is key to diagnosing and managing arrhythmias effectively.

Prevalence in the United States

According to the American Heart Association, millions of people in the United States have arrhythmias. These conditions become more common with age, and are often seen in people with heart disease. The exact prevalence can vary depending on the type of arrhythmia and the population being studied.

Type of Arrhythmia	Prevalence	Severity
Atrial Fibrillation	Common, specially in older adults	Can be serious, increasing stroke risk
Ventricular Tachycardia	Less common, often associated with heart disease	Can be life-threatening
Supraventricular Tachycardia	Can occur in anyone, often benign	Usually not life-threatening but can be distressing

By understanding the basics of cardiac arrhythmias, we can better appreciate their importance. This knowledge is key for creating effective management and treatment plans.

Types of Arrhythmias and Their Varying Severity

It’s important for doctors to know about the different types of arrhythmias and how serious they are. Arrhythmias are irregular heartbeats. They can be classified into several types based on their characteristics and where they happen in the heart.

Tachycardias (Fast Heart Rhythms)

Tachycardias are when the heart beats too fast, over 100 beats per minute. They can be harmless or very dangerous, depending on the cause and symptoms. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) are two types. VT is more serious because it starts in the heart’s ventricles and can cause ventricular fibrillation if not treated quickly.

Bradycardias (Slow Heart Rhythms)

Bradycardias happen when the heart beats too slowly, under 60 beats per minute. A slow heart rate can be normal in athletes but may be a problem for others. Symptomatic bradycardia can cause dizziness, fainting, or even heart failure in severe cases. Sometimes, a pacemaker is needed.

Premature Beats

Premature beats, or extrasystoles, are early electrical impulses that disrupt the heart rhythm. They can feel like skipped beats or palpitations. While often harmless, frequent premature beats can be a sign of heart disease. Premature atrial contractions (PACs) and premature ventricular contractions (PVCs) are the main types, with PVCs being more concerning because they start in the ventricles.

Conduction Disorders

Conduction disorders affect the heart’s electrical pathways, leading to irregular rhythms. Atrioventricular (AV) blockand bundle branch blocks are examples. The severity can range from mild to severe, with third-degree AV block being a serious condition that may need a pacemaker.

The severity of arrhythmias varies widely among different types. Accurate diagnosis and classification are key for the right treatment. “The classification of arrhythmias based on their severity is a critical step in managing patients effectively,” as noted by a leading cardiology guideline. This helps doctors tailor treatments to each patient’s needs, improving outcomes.

Common Symptoms Associated with Arrhythmias

It’s important to know the symptoms of arrhythmias to understand their severity. Arrhythmias, or irregular heartbeats, can show up in different ways. Spotting these symptoms is the first step to managing them well.

Mild Symptoms

Mild arrhythmia symptoms might be hard to notice or not bother your daily life much. These can include:

• Occasional palpitations or skipped beats
• Mild dizziness or lightheadedness
• A feeling of irregular heartbeat

Even though these symptoms might not seem serious, watching them and seeing a doctor if they get worse is key.

Moderate Symptoms

Moderate symptoms show that arrhythmias are affecting the heart more. Symptoms can be:

• Frequent palpitations or irregular heartbeats
• Dizziness or fainting spells
• Shortness of breath or trouble breathing
• Chest discomfort or pain

These signs mean the arrhythmia is impacting the heart’s function more. It’s time to see a doctor.

Severe Symptoms Requiring Immediate Attention

Severe arrhythmia symptoms are serious and need quick medical help. These include:

• Severe chest pain or pressure
• Severe trouble breathing
• Fainting or near-fainting spells
• Rapid or irregular heartbeat that doesn’t respond to treatment

If you or someone else has these symptoms, getting emergency care right away is vital.

To understand how arrhythmia symptoms relate to their severity, check out this table:

Symptom Severity	Common Symptoms	Recommended Action
Mild	Occasional palpitations, mild dizziness	Monitor symptoms, consult a healthcare provider
Moderate	Frequent palpitations, dizziness, shortness of breath	Seek medical evaluation
Severe	Severe chest pain, difficulty breathing, fainting	Seek immediate emergency care

Arrhythmia Severity Assessment: Clinical Approaches

Doctors use many ways to check how serious an arrhythmia is. They use tests and tools to figure out how to manage it best. Let’s dive into these methods to see how they help.

Initial Evaluation Methods

The first step is to talk to the patient and do a physical check-up. This helps find out what might be causing the arrhythmia. Important parts of this step include:

• Talking to the patient to learn about symptoms and family history
• Checking the heart and body for signs of other health issues
• Doing an ECG to see how the heart’s electrical system is working

Diagnostic Tests and Procedures

To get a better look at the arrhythmia, doctors use different tests. These include:

1. Holter Monitoring: A 24- to 48-hour ECG to catch arrhythmias that don’t happen all the time.
2. Event Monitoring: A device that records the heart for weeks to catch arrhythmias.
3. Electrophysiology Studies (EPS): A test that looks at the heart’s electrical system and can make arrhythmias happen on purpose.

These tests help doctors understand the arrhythmia better. This helps them decide the best treatment.

Risk Stratification Tools

It’s important to know how serious an arrhythmia is and if it could get worse. Doctors use tools like:

• Risk scores that look at age, other health problems, and the arrhythmia itself
• Biomarkers that show if the heart is stressed or damaged

These tools help doctors sort patients by how much risk they have. This way, they can plan the best care for each person.

The Role of Cardiac Imaging

Cardiac imaging is key in checking how serious an arrhythmia is. It shows what the heart looks like and how it works. Tests like echocardiography, MRI, and CT scans help find problems like heart disease that might cause arrhythmias.

By using all these methods together, doctors can really understand how serious an arrhythmia is. Then, they can make a treatment plan that fits each patient’s needs.

The Arrhythmia Severity Classification System

The arrhythmia severity classification system is key for doctors to manage arrhythmias well. It helps them see how risky different arrhythmias are. This guides their treatment choices.

Arrhythmias are sorted into levels based on how serious they are. This system helps doctors know who needs urgent care and who can be treated more gently.

Class I (Benign Arrhythmias)

Class I arrhythmias are not very risky. They usually don’t need treatment and can be managed with simple lifestyle changes.

Class II (Moderately Serious Arrhythmias)

Class II arrhythmias are a bit more serious. They might need medical help to avoid problems. These arrhythmias can affect a person’s daily life and need regular checks.

Class III (Serious Arrhythmias)

Class III arrhythmias are quite serious. They need quick medical help. These arrhythmias can really harm a person’s health and might need strong treatments.

Class IV (Life-Threatening Arrhythmias)

Class IV arrhythmias are very dangerous. They need immediate medical care. If not treated right away, they can be deadly.

To show how the system works, here’s a table with the different classes and what they mean:

Class	Severity	Characteristics	Treatment Approach
I	Benign	No significant risk	Lifestyle modifications
II	Moderately Serious	May require medical treatment	Medical treatment, ongoing monitoring
III	Serious	Significant impact on health	Aggressive treatment, medication, interventional procedures
IV	Life-Threatening	Immediate medical attention required	Emergency treatment, prompt intervention

Knowing about the arrhythmia severity system helps us manage arrhythmias better. It’s a key tool for doctors to figure out the risk of different arrhythmias. This helps them make the best treatment plans for patients.

Atrial Fibrillation: Assessing Severity and Risks

Atrial fibrillation is a common heart rhythm problem. It needs a detailed look at its severity and risks. Knowing its types and stroke risk is key to managing it well.

Paroxysmal vs. Persistent vs. Permanent AF

Atrial fibrillation (AF) comes in three types: paroxysmal, persistent, and permanent. Paroxysmal AF stops on its own within seven days. Persistent AF lasts over seven days and might need treatment. Permanent AF is when the arrhythmia is accepted, focusing on symptom control and preventing complications.

Stroke Risk Assessment in AF

AF increases the risk of stroke. The CHA₂DS₂-VASc score helps assess this risk. It looks at factors like heart failure, high blood pressure, age, diabetes, and more. This score helps decide if anticoagulation therapy is needed to prevent stroke.

Quality of Life Impact

Atrial fibrillation can greatly affect a patient’s life. Symptoms like palpitations, shortness of breath, and fatigue vary in severity. Managing AF means treating the arrhythmia and improving the patient’s quality of life.

CHA₂DS₂-VASc Score Explained

The CHA₂DS₂-VASc score predicts stroke risk in AF patients. It scores points for factors like heart failure, high blood pressure, age, diabetes, and more. A higher score means a higher stroke risk, helping decide on anticoagulant therapy.

Understanding AF severity and using the CHA₂DS₂-VASc score helps manage the condition. It reduces complications and improves patients’ quality of life.

Ventricular Arrhythmias and Sudden Cardiac Death Risk

Ventricular arrhythmias are a big threat to heart health. They can lead to sudden cardiac death. These arrhythmias start in the heart’s ventricles and can be mild or very dangerous. We will talk about how serious these arrhythmias are, how to predict the risk, and why care after a cardiac arrest is key.

Ventricular Tachycardia Severity Levels

Ventricular tachycardia (VT) is a fast heart rate that starts in the ventricles. The severity of VT can vary. Some episodes are short and don’t cause symptoms, while others can be very serious.

• Non-sustained VT: Lasts less than 30 seconds and typically does not cause significant symptoms.
• Sustained VT: Lasts more than 30 seconds and can lead to hemodynamic instability.
• VT with cardiac arrest: Can lead to sudden cardiac death if not treated promptly.

Ventricular Fibrillation as a Medical Emergency

Ventricular fibrillation (VF) is a serious arrhythmia that needs quick medical help. It’s when the heart’s ventricles quiver fast, causing cardiac arrest.

Key aspects of VF:

1. Immediate recognition and treatment are critical.
2. Cardiopulmonary resuscitation (CPR) and defibrillation are essential.
3. VF can happen after a heart attack or other heart problems.

Risk Prediction Models

There are risk prediction models to guess the chance of sudden cardiac death in patients with ventricular arrhythmias. These models look at things like:

• Left ventricular ejection fraction (LVEF)
• History of myocardial infarction
• Presence of heart failure
• Electrophysiological study results

Examples include the MADIT and MUSTT scores.

Post-Cardiac Arrest Care

After a cardiac arrest, it’s important to get the right care to prevent it from happening again. This includes:

• Targeted temperature management: To reduce neurological damage.
• Coronary angiography: To find and treat heart artery disease.
• Implantable cardioverter-defibrillator (ICD) placement: To stop sudden cardiac death.

In conclusion, ventricular arrhythmias are a big risk for sudden cardiac death. Knowing how serious they are, using risk models, and giving good care after a cardiac arrest are key to managing them well.

Supraventricular Arrhythmias: When to Worry

Supraventricular arrhythmias, like supraventricular tachycardia (SVT), affect the heart’s rhythm. They can be serious. These heart rhythm problems start above the ventricles and worry those who have them.

Types and Severity

There are many types of supraventricular tachycardias, each with its own traits and severity. The most common include:

• Atrioventricular nodal reentrant tachycardia (AVNRT)
• Atrioventricular reentrant tachycardia (AVRT)
• Atrial tachycardia
• Sinus node reentrant tachycardia

These conditions can be mild or very serious. Knowing the type and how severe it is helps decide the best treatment.

Impact on Daily Life

Supraventricular arrhythmias can greatly affect daily life. Symptoms include palpitations, shortness of breath, chest pain, and dizziness. How often and how bad these symptoms are can differ a lot.

For some, SVT episodes are rare and mild, barely affecting their life. But for others, episodes can happen often, be very bad, and really mess up their daily life and how well they feel.

Long-term Prognosis

The long-term outlook for people with supraventricular arrhythmias depends on several things. These include the type and how often episodes happen, the heart’s overall health, and how well treatment works.

With the right treatment and care, many people with SVT can live active and normal lives. But, it’s key to work closely with doctors to create a treatment plan that fits you. Also, keep an eye on your condition over time.

Heart Block: Grading System and Severity

The grading system for heart block helps doctors understand how serious it is. It shows how well the heart’s electrical signals work. Heart block happens when these signals don’t reach the heart’s lower chambers on time.

First-Degree AV Block

First-degree AV block means the electrical signal is delayed. But, all signals get to the ventricles. This usually doesn’t cause symptoms and might not need treatment, just watching it.

Second-Degree AV Block (Mobitz Type I and II)

The second-degree AV block has two types: Mobitz Type I (Wenckebach) and Mobitz Type II. Type I shows a longer PR interval before a beat is missed. Type II has a consistent PR interval but sometimes misses a beat without a long interval first. Mobitz Type II is more serious because it can get worse.

Third-Degree (Complete) AV Block

Third-degree AV block means no signals from the atria reach the ventricles. The ventricles beat on their own, which might be too slow. A pacemaker is often needed to keep the heart rate up.

Bundle Branch Blocks

Bundle branch blocks slow down the electrical signals in the ventricles. They can happen in the left or right bundle branch. Even though they might not cause symptoms, they can show heart disease and lead to more serious problems.

Knowing the type and severity of heart block is key to choosing the right treatment. Some types are mild and need little action. But others are serious and need quick medical help.

Risk Factors That Increase Arrhythmia Severity

Knowing what makes arrhythmias worse is key to managing them well. Several factors can make arrhythmias more severe. These include heart diseases and other health issues. We’ll look into these factors to understand their impact.

Structural Heart Disease

Heart diseases that change the heart’s shape or function can lead to arrhythmias. For example, heart valve problems or coronary artery disease can make the heart beat irregularly. This is because the heart’s electrical pathways are affected.

Examples of structural heart disease include:

• Coronary artery disease
• Heart valve disorders
• Cardiomyopathy
• Congenital heart defects

Comorbid Conditions

Having other health issues along with arrhythmias can make them worse. Conditions like diabetes, high blood pressure, and thyroid problems can complicate treatment. For instance, diabetes can damage nerves that control heart rhythm, while high blood pressure can change the heart’s shape, leading to arrhythmias.

Comorbid Condition	Impact on Arrhythmia Severity
Diabetes	Nerve damage affecting heart rhythm
Hypertension	Changes in heart structure
Thyroid disorders	Altered metabolic rate affecting heart function

Genetic Factors

Genetics play a big role in some arrhythmias. If your family has a history of arrhythmias, you might be at higher risk. Genetic tests can help identify those at risk and guide preventive steps.

Genetic conditions that can lead to arrhythmias include:

• Long QT syndrome
• Brugada syndrome
• Hypertrophic cardiomyopathy

Medication Interactions

Some medicines can make arrhythmias worse or interact with treatments. It’s important to tell your doctor about all the medicines you take. For example, some drugs can lengthen the QT interval, raising the risk of arrhythmias.

Understanding these risk factors helps us manage arrhythmias better. Effective management includes treating underlying conditions, avoiding triggers, and following treatment plans.

Advanced Diagnostic Technologies for Arrhythmia Severity Assessment

New technologies have changed how we diagnose and treat arrhythmias. These tools help us better understand how severe arrhythmias are. This makes it easier to find the right treatment.

Continuous Monitoring Devices

Devices for long-term monitoring are key in managing arrhythmias. Wearable monitors and implantable loop recorders track heart rhythms over time. They catch arrhythmias that might not show up in short tests.

Benefits of Continuous Monitoring:

• Captures intermittent arrhythmias
• Provides real-time data for timely intervention
• Enhances patient comfort and compliance

Electrophysiology Studies

Electrophysiology studies (EPS) are detailed tests that look at the heart’s electrical system. They map the heart’s electrical paths. This helps find where arrhythmias start and guides treatment.

The Role of EPS in Arrhythmia Management:

1. Diagnoses complex arrhythmias
2. Guides catheter ablation procedures
3. Assesses the risk of future arrhythmic events

Genetic Testing

Genetic testing helps understand the risk and severity of some arrhythmias. It finds genetic mutations that increase risk. This lets doctors tailor treatments.

Genetic Condition	Arrhythmia Risk	Management Strategy
Long QT Syndrome	High risk of life-threatening arrhythmias	Beta-blocker therapy, ICD implantation
Brugada Syndrome	Increased risk of ventricular fibrillation	ICD implantation, avoidance of certain medications

AI-Based ECG Analysis

Artificial intelligence (AI) is making ECG analysis better. AI finds patterns in ECGs that show how severe arrhythmias are. This makes diagnosis more accurate.

Using these advanced tools, we can better manage arrhythmias. This leads to better health outcomes for patients.

Treatment Approaches Based on Arrhythmia Severity

The severity of arrhythmias determines the treatment. Options range from watching closely to using devices. We’ll look at how to manage arrhythmias based on their severity.

Observation for Mild Arrhythmias

For mild arrhythmias, a careful watch is often enough. This means keeping an eye on the condition and making lifestyle changes. These changes can help manage symptoms and keep the heart healthy.

Medication Therapies

For more serious arrhythmias, medicine is key. Anti-arrhythmic drugs help control the heart’s rhythm. The right medicine depends on the arrhythmia type, its severity, and the patient’s health.

Interventional Procedures

For some arrhythmias, procedures are a good choice. Catheter ablation is a small procedure that fixes the heart’s electrical issues. Other methods, like cardioversion, can also help.

Implantable Devices

For severe or dangerous arrhythmias, devices like pacemakers or implantable cardioverter-defibrillators (ICDs) are used. These devices keep the heart rhythm steady and can stop sudden death by shocking the heart when needed.

Here’s a quick look at how to treat arrhythmias based on their severity:

Arrhythmia Severity	Treatment Approach	Key Interventions
Mild	Observation and Lifestyle Adjustments	Regular monitoring, lifestyle changes
Moderate	Medication Therapies	Anti-arrhythmic drugs
Severe	Interventional Procedures and Implantable Devices	Catheter ablation, pacemakers, ICDs

Healthcare providers tailor treatments to each patient’s needs. This way, they can manage arrhythmias well and improve outcomes.

Psychological Impact and Quality of Life Considerations

Living with an arrhythmia can be tough, affecting both mind and body. It can really change how you feel, causing anxiety, depression, and more. These feelings can make everyday life harder.

Anxiety and Depression in Arrhythmia Patients

People with arrhythmias often feel more anxious and depressed. The unpredictable nature of arrhythmia episodes can add to stress. This stress can affect daily life and mental health.

Key statistics:

Condition	Prevalence in Arrhythmia Patients	Prevalence in General Population
Anxiety	30-40%	19.1%
Depression	20-30%	7.1%

Coping Strategies

Finding ways to cope is key for managing arrhythmia’s mental effects. Patients can benefit from:

• Mindfulness and meditation
• Cognitive-behavioral therapy (CBT)
• Support groups
• Regular physical activity

These methods can help lessen anxiety and depression. They can also improve overall quality of life.

Support Resources

It’s important for arrhythmia patients to have the right support. This includes:

• Healthcare providers specializing in cardiology
• Patient support groups
• Online forums and communities
• Educational materials and workshops

These resources offer emotional support, practical advice, and useful information. They help manage arrhythmias better.

Impact on Daily Activities

Arrhythmias can affect daily life a lot. They can impact work, social life, personal care, and leisure activities. Patients might need to make lifestyle changes to manage their condition well.

Common challenges include:

• Reduced physical stamina
• Increased stress and anxiety
• Uncertainty about when symptoms may occur

Understanding these challenges and using the right coping strategies can improve quality of life. It helps manage the psychological impact of arrhythmias better.

Living with Arrhythmias: Lifestyle Modifications

Making lifestyle changes is key to controlling arrhythmias and improving life quality. By changing our daily habits, we can greatly improve our heart health. This can also lessen the severity of arrhythmia symptoms.

Diet and Nutrition

Eating a heart-healthy diet is important. It should include lots of fruits, vegetables, whole grains, and lean proteins. Try to eat less of saturated fats, cholesterol, and sodium.

Increasing omega-3 fatty acid consumption through foods like salmon and sardines is also good.

A health expert says, “A diet rich in omega-3 fatty acids can help reduce inflammation and improve heart health.”

“The Mediterranean diet, which is high in fruits, vegetables, and healthy fats, has been shown to reduce the risk of heart disease.”

Exercise Recommendations

Regular exercise is great for managing stress and improving heart health. Aim for at least 150 minutes of moderate-intensity aerobic exercise each week. Good options include brisk walking, cycling, or swimming.

Stress Management

High stress levels can make arrhythmia symptoms worse. Practices like meditation, deep breathing, and yoga can help. Establishing a regular relaxation practice can also boost well-being.

• Meditation and mindfulness practices
• Deep breathing exercises
• Yoga and tai chi

Sleep Optimization

Getting enough sleep is vital for heart health. Aim for 7-8 hours of sleep per night and stick to a sleep schedule. A sleep-friendly environment can also help improve sleep quality.

By adding these lifestyle changes to our daily routine, people with arrhythmias can manage their condition better. It’s about making lasting changes that support heart health.

When to Seek Emergency Care for Arrhythmias

Knowing when to seek emergency care for arrhythmias is key. Arrhythmias can be mild or serious. It’s important to know when to act fast to avoid serious problems.

Red Flag Symptoms

Some symptoms mean you need to see a doctor right away. These include:

• Chest pain or discomfort
• Shortness of breath
• Dizziness or fainting
• Rapid or irregular heartbeat
• Severe fatigue

If you have any of these symptoms, don’t wait. Call emergency services or have someone drive you to the emergency room if symptoms are severe.

Emergency Response Plan

Having a plan for emergencies is very helpful. This plan should include:

Step	Action
1	Recognize red flag symptoms
2	Call emergency services or seek immediate transportation to the ER
3	Administer any prescribed emergency medication
4	Provide healthcare providers with your medical history and current medications

Communication with Healthcare Providers

Talking to your healthcare providers is important. Make sure to:

• Tell your healthcare team about your arrhythmia and any changes.
• Keep a record of your symptoms and how long they last.
• Ask any questions or share concerns with your healthcare provider.

What to Expect in the Emergency Room

When you get to the emergency room, here’s what you can expect:

• Immediate evaluation by healthcare professionals.
• Monitoring of your heart rhythm and other vital signs.
• Administration of appropriate treatments, which may include medication or cardioversion.
• Diagnostic tests to determine the cause of your symptoms.

Being prepared and knowing what to expect can help reduce stress. Understanding the signs and having a plan can help manage your arrhythmia better.

Conclusion: Managing Arrhythmia Concerns

Managing arrhythmias means knowing how serious they are and what treatment works best. We’ve looked at different types of arrhythmias, their signs, and how doctors check their severity. This knowledge helps people get the right treatment, like medicines, procedures, or devices.

Changing your lifestyle is also key. This includes eating right, exercising, managing stress, and getting enough sleep. These steps can help lower arrhythmia worries and boost heart health. Working with doctors to create a treatment plan is part of managing heart rhythm disorders.

Being proactive in managing arrhythmias can lower risks and enhance life quality. It’s vital to see a doctor if symptoms don’t go away or get worse. With the right care and lifestyle changes, people can handle their arrhythmia issues and keep their heart rhythm healthy.

FAQ

Reference

Nature. Evidence-Based Medical Insight. Retrieved from https://www.nature.com/articles/s41598-025-93906-5

Nature. Evidence-Based Medical Insight. Retrieved from https://www.nature.com/articles/nm.4354