Master the Boards USMLE Step 2 CK, Seventh Edition

Introduction

About the USMLE Step 2 CK Examination

The USMLE Step 2 CK (Clinical Knowledge) is typically taken as the second test in a series of 3 certifying examinations that are necessary to obtain a license to practice medicine in the United States. Step 2 CK is usually taken in medical school at the end of year 3 or during year 4. 

Step 2 CK is more clinically based than Step 1. Although there is no requirement to take Step 1 before Step 2 CK, that is the typical sequence for U.S. graduates. According to the test maker, the questions on Step 2 CK measure the ability to apply medical knowledge, skills, and understanding of clinical science as they pertain to patient care (under supervision), with emphasis on health promotion and disease prevention. 

The most common mistake in preparation is doing the same single question bank over and over! Do as many different questions as you can.

Step 2 CK Examination Structure

USMLE Step 2 CK is a computer-based test that will not exceed 318 questions taken over a 9-hour period. 

Eight blocks of maximum 40 questions, each block 60 minutes

Once you have completed a block or 60 minutes has run out, you will not be able to go back to any questions in that block.

The total break time throughout the day will be 45 minutes. The computer will keep track of your break time. Be sure not to exceed the 45 minutes or you will be penalized by having time deducted from your last block of the test.

USMLE Step 2 CK uses 2 types of questions: single best answer (most common type) and sequential.

USMLE Step 2 CK questions have to be unequivocally clear. If an area is controversial, USMLE will avoid it, and ask only what is clear. The exam will not trick you.

Single Best Answer

The majority of Step 2 CK questions are multiple-choice questions that follow a clinical vignette. The basic structure is:

History of present illness

Physical examination

Possibly laboratory and radiologic tests

There are 5 basic question types (and consequently, the very structure around which this book is created):

What is the most likely diagnosis?

What is the best initial diagnostic test?

What is the most accurate diagnostic test?

What physical finding is most likely to be associated with this patient?

What is the best initial therapy?

When the question reads: "What is the most appropriate next step in management? this can refer to a test or a treatment. The phrase most appropriate next step" can also be referred to as action, management, or simply what should you do next? 

The phrase most appropriate can be very difficult to interpret. It is not always clear whether it means first, best, or most accurate.

The most frequently asked question on Step 2 CK is "What is the most likely diagnosis? As a result, many of the chapters in this book have a specific section labeled What is the most likely diagnosis?" One of the many unique attributes of the Master the Boards format is that the diseases are presented with the specific goal of answering these questions.

Sequential

A smaller number of Step 2 CK questions are multiple questions that follow a single clinical story or vignette. Once you answer the first question, you will not be able to go back to the original question. That is because the second and third questions may give a clue to the answer to the first question. 

Some of the questions in the sequence are matching questions, i.e., 4 and 26 separate answers are presented, and you must select the most appropriate one(s). Several cases may use the same answers. The answers can be used once, more than once, or not at all.

Score Reporting

You must answer 60–70% of questions correctly to get a passing score. 

Your correct answers are converted to a 3-digit score. 

Score reports and transcripts will show your 3-digit score and either Pass or Fail.  Score reports (but not transcripts) will also show your performance on certain topics, intended to help you assess your strengths and weaknesses.

As of publication, the 3-digit passing score was 214, but that score does (and will) increase over time. The reason is simple: Current medical students continue to improve their knowledge. The average score is currently 245, but that will also rise as students improve their knowledge. 

In 2022, the USMLE Step 1 exam moved to a pass/fail score. This raises the stakes for Step 2 CK enormously: it is the only chance you have to distinguish yourself from other candidates with a high score.

There are always a number of new or experimental questions on each exam to test new questions for future exams. Every attempt is made to keep the exam fair and ensure it serves as an accurate measure of your knowledge level.

Registration

For the most accurate and up-to-date information about registration and Test Day procedures, go to usmle.org. At the time of publication, the registration fee is $660 for U.S. medical students and $985 for IMGs.

When to Take Step 2 CK

Frequently, medical students wonder when they should take Step 2 CK. The answer to that question depends on your background and level of knowledge.

Remember, U.S. graduates do not have to take Step 2 CK in order to participate in the annual residency match. However, international graduates must take Step 2 CK to be ECFMG-certified, a requirement to participate in the match.

The vast majority of U.S. graduates take Step 1 at the end of year 2 of medical school.

– Some schools require students to pass Step 1 in order to be allowed into year 3 and clinical rotations.

– Some international schools—particularly those in the Caribbean in which virtually the entirety of the class is headed for residency in the United States—follow this pattern as well.

– Here is the bottom line: if there is no score on USMLE Step 1, it means the only chance you have to distinguish yourself from the other candidates is Step 2, making this test an enormously high-stakes exam.

Timing can be a factor for some U.S. graduates, too. For example, if you have a great Step 1 score and you are applying to a moderately competitive specialty, you may want to delay your Step 2 CK exam until after you have applied and interviewed for residency. The next section looks at some hypothetical scenarios.

Residency and the Exam

Another frequently asked question is, How late can I take Step 2 CK and still be competitive in the match? The Electronic Residency Application Service (ERAS) opens for applications in September. 

To be competitive, plan on having your application complete by the middle of September.

You may think that program directors are sitting in their offices on opening day waiting for applications to come in over ERAS so they can give out interviews. That is not true.

Many programs do not consider an application complete until they have received every single part of the application. Often, the Medical School Performance Evaluation (MSPE) does not go out from U.S. schools until October and, in some cases, November.

If you think it is better to fail than to pass with a low grade, you are wrong. You cannot hide the grade on previous attempts at Step 2 CK. It is better to delay your test than to risk a lower grade. Unfortunately, it is true that if you wait to take Step 2 CK until September or October, you will lose interview spots. However, if you take the test prematurely and fail or pass with a minimal score, that grade will follow you around through your entire application process. I would go so far as to say that it would be better to sit out a year and fully prepare than take a chance on a failing or low grade.

TIP: Do not take the exam before you are ready. You cannot retake Step 2 CK if you pass with a poor grade. It is better to delay so that you can prepare more than to take the exam ill-prepared.

Students often wonder, Is Step 1 or Step 2 CK more important to my future? Step 1 may be perceived as a harder examination; however, the pass rate for first-time U.S. graduate test takers is about 93%. On the other hand, for many clinically oriented specialties, the perception may be that your performance on a clinically oriented examination such as Step 2 CK is more important than an examination more oriented to basic sciences. Step 2 CK is vastly more important than any other test because it is the only test that has a numeric score.

USMLE is the only worldwide, uniform measure across medical schools.

TIP: Step 2 CK is the only exam with a score. Don’t blow it! This is your main chance to shine.

What Do Program Directors Look For?

Program directors all agree on a few important criteria:

Where you went to school

USMLE Step 2 CK scores

Transcript and MSPE (U.S. graduates)

Visa status (international graduates)

Other criteria such as research, publications, recommendation letters, extracurricular activities, and personal statement are much harder to define and are not universally valued.

Some programs may highly prize research, while others may not even look at your publications until after you arrive for an interview. 

The personal statement often has no value because it says nothing personal or original about you at all. 

Letters of recommendation often all sound the same.

The reason that USMLE carries such importance is because it is the only worldwide, uniform measure across schools.

If you are a U.S. medical student, how do you prove to a program director that you have greater value than a student applying from a school with a very highly prized and famous name? Your USMLE score may be the only thing that gives you an edge. 

If you are from a school with a highly prized and famous name, how do you prove that you are a better applicant than another candidate from a similarly highly prized and famous name school? The answer is your transcript and USMLE score.

If you are an international graduate, how do you overcome the fact that you need a visa or perhaps you are applying as an older graduate? The answer is the same: your USMLE score.

Is this fair? Is it right? The system is generally fair. The test taken by U.S. and international graduates is the same. The test is not graded on a curve. That means that theoretically, everyone taking the test on a particular day could get a 270. Whether or not you think it’s right, one thing we know for sure is that the USMLE is of colossal importance to your professional future.

How Do I Get Clinical Experience?

Nothing makes an international student more anxious than the programmatic requirement for United States Clinical Experience. The truth is, unless you are at an international school that is specifically geared to return you to the United States, you are often simply not going to be able to get this U.S. experience. Do not worry!

Many future doctors obtain residency each year as international graduates without U.S. clinical experience. A high score on Step 2 CK is also far more valuable than some fake experience where you hang around an office. 

How is observing measurable? What did you do there? I know you will get anxious about this. If you can get meaningful U.S. experience, that’s great; however, a higher score on Step 2 CK is always valuable.

An observership or externship is of extremely inconclusive value.

After separating applicants into groups based on where they went to school and for international graduates based on their visa status, the program director often has no readily quantifiable way to assess the applicant. There is enormous pressure to make sure that the pool she selects into the residency is highly qualified. Research, observerships, and clinical grades are hard to measure.

Is one school a harder grader than another?

Does one school practice grade inflation so that all the transcripts show high grades?

Does another school fail many students to prove they are serious?

These are all factors that may be considered. Take time to understand how your credentials stack up.

What If I Failed?

The best way to show that your failure on Step 2 CK is not an accurate measure of your ability, knowledge, or intelligence is to pass with a very high score when you DO pass. 

If you failed Step 1, there is a lot riding on your Step 2 CK grade. This book is constructed to help you pass. 

Take your time. Study day and night. If you need more practice, use question banks to prepare and assess your knowledge base. If necessary, delay the exam until you are ready. 

Several years ago, the size of incoming classes in U.S. medical schools started to increase after more than 30 years with the same class size. In addition, many new schools are opening. 

This has an enormous impact on both U.S. and international graduates. In  prior years, simply being a U.S. graduate automatically put you in the top half of the applicant pool in many specialties. That is no longer true. The incoming class size for U.S. schools will be increasing by several hundred every year for the next several years. This will increase the competition for everyone trying to get a good residency position.

U.S. medical students pass Step 2 CK at a rate of ~93%, doctors of osteopathic medicine (DO) pass at a rate of ~92%, and international graduates pass at a rate of ~71%.

Author’s Note

You have worked very hard to get into medical school and to do well there. This is your last step. A great score on Step 2 CK will mean that all of your professional dreams in medicine are about to come true.

Now is the time to learn everything in this book. You can rest later. Practice hard and remember that everything you are learning here is medicine. It will help people. 

A high grade on Step 2 CK is not a phony numerical statistic. What you are learning here will, with 100% certainty, help someone. You will save lives. You will relieve suffering. You will do good for humanity. It is with this emotional power that you should go forth to work hard and to test the limits of your endurance. 

What you learn here, through your heart and mind and the power of your hands, will protect those who suffer in their hour of need.

I wish you well in your quest. If you see what you are learning here as a bunch of stuff to cram in that you will forget, you will not get as good a grade and the information will quickly fade. If you can study knowing that a sick person that you have not yet met is depending on you, their very life is depending on you, then you will absorb this energy and make the studying you must do an act of devotion.

We—you and I—commit ourselves at this moment to our sacred calling. To offer humanity the best of our art, and to put the needs of others above our own needs, now and always.

Dr. Conrad Fischer

PART 1

Clinical Science

1

Allergy and Immunology

Anaphylaxis

Anaphylaxis is defined as the worst form of allergic condition or acute event. It is synonymous with the term immediate hypersensitivity. 

Anaphylaxis is defined by the severity, not the cause, of the reaction.

Patient must already have been sensitized to the antigen.

IgE binds to mast cells, leading to the release of their granules (e.g., histamine, prostaglandins, and leukotrienes), which results in the abnormalities that essentially define anaphylaxis. 

Anaphylactoid reactions are non-IgE related, are clinically identical and treated the same way, and do not need preceding sensitization to the antigen.

– Respiratory

– Hemodynamic

The causes of anaphylaxis are the same as the causes of any allergic event, such as:

Insect bites and stings

Medications: penicillin, phenytoin, lamotrigine, quinidine, rifampin, sulfa

Foods

Latex is a very important cause of anaphylaxis in healthcare workers.

Figure  1.1 Anaphylaxis

Symptoms include:

Rash (present with any allergic reaction)

Hypotension, tachycardia

Respiratory distress: shortness of breath; wheezing; swelling of the lips, tongue, or face; stridor

There is no specific diagnostic test to define anaphylaxis.

Urticaria is considered part of anaphylaxis, not just an allergy.

Treatment is as follows:

Epinephrine given intramuscularly

Antihistamines such as diphenhydramine (H1-blocker) and cimetidine (H2-blocker)

Glucocorticoids such as methylprednisolone or hydrocortisone

Emergent airway protection if needed: intubation or cricothyroidotomy

Epinephrine injection:

IM for anaphylaxis

IV for ventricular fibrillation/asystole

Angioedema

Angioedema is sudden swelling of the face, tongue, eyes, and airway, commonly due to a deficiency of C1 esterase inhibitor. Onset of angioedema has a characteristic association with minor physical trauma or the recent start of ACE inhibitors. However, ACE inhibitors can trigger angioedema even after years of use.

Angioedema often has an idiopathic origin. 

Hereditary angioedema is characterized by sudden facial swelling and stridor with the absence of pruritus and urticaria. Hereditary angioedema does not respond to glucocorticoids or epinephrine.

ACE inhibitors do not have to be recently started to cause angioedema.

Figure 1.2 Angioedema can swell the eyes shut.

Source: James Heilman, MD, Wikipedia, CC-BY-SA

The best initial tests are decreased C2 and C4 in the complement pathway and deficiency of C1 esterase inhibitor.

Treatment is as follows:

Ensure the airway first, as the process can evolve rapidly.

Acute attack: fresh frozen plasma, ecallantide, or icatibant

Urticaria and early respiratory compromise: epinephrine, antihistamine, steroids

Hereditary angioedema with severe laryngeal involvement: C1 esterase inhibitor concentrate (or recombinant C1 inhibitor concentrate)

Bradykinin B2 receptor antagonist: icatibant

Kallikrein inhibitor: ecallantide

Lanadelumab: antibody against kallikrein

Prophylaxis for surgical and dental procedures, which can precipitate angioedema: 

– Antifibrinolytics (e.g., tranexamic acid): decrease C1 protein and therefore decrease the production of bradykinin

– Androgens (danazol, stanozolol)

– Infusions of C1 esterase inhibitor (recombinant or plasma-derived)

Antihistamines, glucocorticoids, and epinephrine are not effective for angioedema. They are helpful for anaphylaxis—not for C1 esterase inhibitor deficiency.

Figure 1.3 Angioedema Treatment

Urticaria

Urticaria is an allergic reaction that causes sudden swelling of the superficial layers of the skin. Causes include insects, medications, and physical agents such as pressure (dermatographism); cold; and vibration.

Treatment is as follows:

Antihistamines: hydroxyzine, diphenhydramine, fexofenadine, loratadine, or cetirizine plus cimetidine

Leukotriene receptor antagonists: montelukast or zafirlukast

Figure 1.4 Urticaria, Localized Anaphylaxis with a Wheal and Flare

Source: Farshad Bagheri, MD

Allergic Rhinitis

Seasonal allergies such as hay fever are common. This is an IgE-dependent triggering of mast cells. Symptoms include recurrent episodes of:

Watery eyes, sneezing, itchy nose, and itchy eyes

Inflamed, boggy nasal mucosa

Pale or violaceous turbinates

Nasal polyps

Allergic rhinitis is most often a clinical diagnosis with recurrent episodes of the presentation previously described. Skin testing and blood testing for reactions to antigens may be useful to identify a specific etiology. Allergen-specific IgE levels may be elevated.

Nasal smear may show large numbers of eosinophils.

Treatment

Prevention, with avoidance of the precipitating allergen

– Close windows and use air conditioning to avoid pollen

– Get rid of animals to which the patient is allergic

– Cover mattresses and pillows

– Use air purifiers and dust filters

Intranasal corticosteroid sprays

Antihistamines: loratadine, clemastine, fexofenadine, brompheniramine

Intranasal anticholinergic medications: ipratropium

Desensitization to allergens that cannot be avoided

Primary Immunodeficiency Disorders

Common Variable Immunodeficiency (CVID)

In CVID, B cells are present in normal numbers, but they do not make sufficient amounts of immunoglobulins. There is a decrease in all the subtypes: IgG, IgM, and IgA. There is also a decreased response to antigen stimulation of B cells.

CVID presents with recurrent sinopulmonary infections in adults. Rates of incidence are equal in men and women. Bronchitis, pneumonia, sinusitis, and otitis media are common, as are:

Giardiasis

Spruelike intestinal malabsorption

Increases in autoimmune diseases such as pernicious anemia and rheumatic diseases

TIP: The clues to CVID are a reduced output of B lymphocytes, a normal number of B cells, and a normal amount of lymphoid tissue (e.g., nodes, adenoids, and tonsils).

Test quantitative levels of serum immunoglobulin to establish diagnosis of CVID:

IgG level will be low.

IgA or IgM may also be low.

Treat each infection as it arises with antibiotics. Chronic maintenance for CVID is with regular infusions of IV immunoglobulins.

X-Linked (Bruton) Agammaglobulinemia

X-linked agammaglobulinemia presents in male children with increased sinopulmonary infections. B cells and lymphoid tissues are diminished. There is a decrease or absence of the tonsils, adenoids, lymph nodes, and spleen. T cells are normal. 

Treatment is management of the infections as they arise. Long-term, regular administration of IVIG keeps these children healthier.

Severe Combined Immunodeficiency

The word combined in severe combined immunodeficiency (SCID) means that there is deficiency in both B and T cells. This results in infections related to both deficiencies.

B cells: decreased immunoglobulin production leads to recurrent sinopulmonary infection beginning as early as age 6 months 

T cells: markedly decreased numbers of T cells give many of the infections that you would see with AIDS patients, e.g., PCP, varicella, and Candida

Treat the infections as they arise; in addition, these patients should undergo a bone marrow transplant, which can be curative.

IgA Deficiency

These patients also present with recurrent sinopulmonary infections. The difference between this syndrome and the others is:

Atopic diseases

Anaphylaxis to blood transfusion when blood is given from a patient who has normal levels of IgA

Spruelike condition with fat malabsorption

Increase in the risk of vitiligo, thyroiditis, and rheumatoid arthritis

Treatment is management of the infections as they arise.

Use only blood that is from IgA-deficient donors or has been washed.

Intravenous immunoglobulin (IVIG) injection will not work because the amount of IgA is too low to be therapeutic. 

Trace amounts of IgA in IVIG may provoke anaphylaxis in the same way that a blood transfusion does.

Hyper IgE Syndrome

This presents with recurrent skin infections with Staphylococcus. Treat these infections as they arise and consider prophylactic antibiotics such as dicloxacillin or cephalexin.

Wiskott-Aldrich Syndrome

This is an immunodeficiency combined with thrombocytopenia and eczema. T lymphocytes are markedly deficient in the blood and the lymph nodes. Bone marrow transplantation is the only definitive treatment.

Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a genetic disease resulting in extensive inflammatory reactions. The result is lymph nodes with purulent material leaking out. 

Aphthous ulcers and inflammation of the nares are common. Granulomas may become obstructive in the GI or urinary tract.

Test for dihydrorhodamine in chronic granulomatous disease.

What Is the Most Likely Diagnosis?

Look for infections with the odd combination of:

Staphylococcus

Burkholderia

Nocardia

Aspergillus

Diagnostic testing:

Abnormal results of nitroblue tetrazolium testing or dihydrorhodamine testing detect the decrease in the respiratory burst that produces hydrogen peroxide. 

This is a decrease in NADPH oxidase, which generates superoxide.

2

Cardiology

Syncope

Syncope is loss of consciousness due to insufficient blood flow to the brain. Cardiovascular problems are one cause, but syncope can also arise from neurological causes or from toxins or metabolic problems.

The first step in the evaluation of loss of consciousness from syncope is to confirm that the patient has definitely lost consciousness. Just because a person falls to the floor or is less responsive does not mean there is syncope. Evaluate loss of consciousness as follows:

Was the loss of consciousness sudden or gradual?

Sudden loss usually has a cardiac or neurologic etiology, such as arrhythmia or seizure.

Gradual loss usually stems from toxins or metabolic problems, such as hypoglycemia, hypoxia, or drug intoxication.

Vasovagal syncope can be sudden or gradual in onset.

Was the regaining of consciousness sudden or gradual?

Sudden regaining usually has a cardiac etiology, such as arrhythmia, valve disease, or ischemia.

Gradual regaining usually stems from tonic-clonic, generalized seizures (exception: absence seizure).

Patients with true syncope are not able to hear people speaking. Urinary or bowel incontinence is too nonspecific to be useful.

Note that people do not seize and wake up right away. They have a post-ictal state of confusion that can last up to 24 hours.

If the loss and regaining are both sudden, the next step is a cardiac exam as follows:

Exam normal: arrhythmia, needs EKG, telemetry monitor, and troponin level

Exam abnormal: needs echocardiogram; exclude AS, HOCM, MS

Figure 2.1 Syncope Evaluation

Treatment of syncope is based on the history and physical examination. Routinely get a head CT, EKG, cardiac enzymes, and echocardiogram. 

Those inpatient are placed on cardiac telemetry to monitor for an arrhythmia. 

Those discharged home have a Holter (long-term EKG) placed for the same purpose. These cardiac monitors can often be worn for months or implanted as a loop recorder.

Additional management of syncope may be indicated.

Recurrent vasovagal syncope

– Test with counterpulsion measures: have the patient lie supine, raise the legs, and tense the muscles of the abdomen; have the patient cross the legs and tense the arms or use handgrip

Brugada syndrome

– Syncope or sudden cardiac arrest in someone of Asian origin; often precipitated by stimulant (e.g., fever)

– Look for right bundle branch pattern on EKG

– Most accurate test: electrophysiological (EP) study

– Treat with AICD placement

Baroreceptor (carotid sinus) hypersensitivity syndrome

– Lightheadedness or loss of consciousness because of pressure on the neck

– More often in older persons with atherosclerotic disease

– Look for lightheadedness while shaving, putting on a tie, or fastening the chin strap of a helmet

– Test by pressing on carotids and looking for sinus pause or drop in BP

– Manage with pacemaker placement or alpha agonist (e.g., midodrine)

90% of mortality from syncope is due to cardiac causes.

Coronary Artery Disease

Coronary artery disease (CAD) (also called atherosclerotic or ischemic heart disease) describes insufficient perfusion of the coronary arteries due to an abnormal narrowing of the vessels, resulting in insufficient oxygen delivery to the myocardial tissue.

When chest pain is equivocal or the history is uncertain, understanding the risk factors is critical for establishing a diagnosis of CAD. The most clearly agreed-upon risk factors for CAD are:

DM (most serious)

Hypertension (most common)

Family history of premature CAD

Hyperlipidemia

Tobacco smoking

Age >45 (men) and age >55 (women)

Renal disease

The presence of CAD risk factors can help answer the question, Which of the following is the most likely diagnosis? when the patient is young or the presentation is equivocal.

Diabetes Mellitus

When followed over a long period of time (e.g., 10 years), it has been found that patients with DM have the highest rates of CAD. 

Hypertension

Hypertension (BP >140/90 mm Hg) is more common than DM, with ~20% of the total U.S. population (60 million people) suffering from hypertension. Nearly 50% of these people are unaware that they are hypertensive.

Family History of Premature CAD

Only premature CAD in a first-degree relative (sibling or parent) is a risk factor for CAD. Premature CAD is defined as male relative age <55 or female relative age <65.

In other words, if CAD developed in older adult relatives or if the relatives were grandparents, cousins, or aunts/uncles, there is no specific risk factor for CAD.

On the exam, the most common mistake about risk factor involves family history, i.e., students mistake CAD in older relatives (including their own parents) as a risk factor. The key is that the CAD in a relative must be premature.

TIP: Menstruating adults virtually never have myocardial infarction.

TIP: Overall, more women will die of heart disease than men.

Stress-Induced (Takotsubo) Cardiomyopathy

A postmenopausal woman develops chest pain immediately on hearing the news of her son’s unexpected death. She develops acute chest pain, dyspnea, and ST segment elevation in leads V2 to V4 on EKG. Elevated troponin confirms an acute myocardial infarction. Coronary angiography is normal including an absence of vasospasm on provocative testing. EKG reveals apical left ventricular ballooning. What is the presumed mechanism of this disorder?

Absence of estrogen

Massive catecholamine discharge

Plaque rupture

Platelet activation

Emboli to the coronary arteries

Answer: B. Takotsubo cardiomyopathy is acute myocardial damage most often occurring in postmenopausal women immediately following an overwhelming, emotionally stressful event. Examples are divorce, financial issues, earthquake, lightning strike, and hypoglycemia. This leads to ballooning and left ventricular dyskinesis. As with ischemic disease, manage with beta blockers and ACE inhibitors. Revascularization will not help, since the coronary arteries are normal.

Sudden, overwhelming emotional stress and anger can cause chest pain and sudden death.

Correcting which of the following risk factors for CAD will result in the most immediate benefit for the patient?

Diabetes mellitus

Tobacco smoking

Hypertension

Hyperlipidemia

Weight loss

Answer: B. Smoking cessation results in the greatest immediate improvement in patient outcomes for CAD. Within 1 year after stopping smoking, the risk of CAD decreases by 50%, and within 2 years after stopping smoking, risk is reduced by 90%.

Chest Pain Presentation

What Is the Most Likely Diagnosis?

For every 100 people presenting to the ED with chest pain:

<10% end up having a myocardial infarction as the cause

≥50% have no cardiac disease at all

The heart is a muscle, and like any muscle, when it is starved for oxygen it will produce a sore-muscle type of pain when ischemic. Ischemic pain is described as:

Dull or sore

Squeezing or pressure-like

Qualities of the pain that go against ischemia are:

Sharp (knifelike) or pointlike

Lasts for a few seconds

Three features of chest pain effectively rule out ischemia as the cause of the pain:

Changes with respiration (pleuritic)

Changes with position of the body

Changes with touch of the chest wall (tenderness)

Ischemic pain is not tender, positional, or pleuritic, so any one of these features would exclude ischemia as a cause of the chest pain (~95% negative predictive value). On the USMLE exam, a 95% negative predictive value is generally enough to allow you to answer the question correctly. When the pain is described as changing with respiration, with bodily position, or upon touching the chest wall, do not answer ischemia or CAD as the cause of the chest pain.

GI disorder is the most common non-ischemic cause of chest pain.

Figure 2.2 Chest Pain Algorithm

TIP: Ischemia versus infarction: Ischemia, or simply decreased perfusion, will be detected by seeing a reversal of the decrease in thallium uptake or wall motion that will return to normal after a period of rest.

There are some nonspecific symptoms of chest pain that will not be helpful in determining a diagnosis.

Nausea

Fever (suggests PE or pneumonia as the cause)

Sweating (diaphoresis)

Anxiety

Diagnostic Tests

Electrocardiogram (EKG) (best initial test for all forms of chest pain)

– In the office-based, ambulatory setting, the EKG is normal most of the time.

Enzymes (CK-MB/troponin)

– In the office-based, ambulatory setting, cardiac enzymes are not the answer when evaluating chronic or stable chest pain.

– In the ED when you are evaluating acute cases of chest pain, enzymes should be used, after the EKG.

Stress (exercise-tolerance) testing

– Exercise tolerance testing (ETT) is indispensable for evaluating chest pain when etiology is not clear and EKG is not diagnostic. 

– ETT is based on 2 factors

Factor 1: You can read the EKG; ischemia is detected by ST segment depression on the EKG (if EKG cannot be read due to a baseline abnormality, do nuclear isotope uptake [thallium or sestamibi] or echocardiographic detection of wall motion abnormalities to detect ischemia)

Factor 2: Patient can exercise, i.e., can increase heart rate >85% of maximum (maximum heart rate = 220 minus the patient’s age)

Alternate methods for increasing myocardial oxygen consumption if patient cannot exercise

– Dipyridamole or adenosine plus a nuclear isotope such as thallium or sestamibi

– Dobutamine plus echocardiogram

Dobutamine will increase myocardial oxygen consumption and provoke ischemia detected as wall motion abnormalities on echo (i.e., dyskinesia, hypokinesia)

Contraindications to dobutamine include ventricular arrhythmias, severe hypertension, LV outflow obstruction, beta blocker

In office/ambulatory clinic, when chest pain for days/weeks: no enzymes

In ED, when chest pain for minutes/hours: yes enzymes

Stress testing is used when the etiology of chest pain is uncertain and the EKG is not diagnostic.

Dipyridamole may provoke bronchospasm. Avoid in asthmatics.

TIP: Baseline EKG abnormalities may be caused by left bundle branch block, left ventricular hypertrophy, pacemaker use, and the effect of digoxin.

Normal myocardium will pick up nuclear isotopes such as thallium in the same way that potassium is picked up by the sodium/potassium ATPase. If the myocardium is alive and perfused, thallium or other nuclear isotopes will be picked up. Abnormalities on echocardiogram will be detected by seeing decreased thallium uptake.

Normal myocardium will move on contraction. Abnormalities will be detected by seeing decreased wall motion. This is also referred to as dyskinesis, akinesis, or hypokinesis.

Ischemia gives reversible wall motion or thallium uptake between rest and exercise. Infarction is irreversible, or fixed.

A man with atypical chest pain is found to have normal nuclear isotope uptake in his myocardium at rest. On exercise, there is decreased uptake in the inferior wall. Two hours after exercise, the uptake of nuclear isotope returns to normal. What is the next step in management?

Coronary angiography

Bypass surgery

Percutaneous coronary intervention (e.g., angioplasty)

Dobutamine echocardiography

Nothing; it is an artifact

Answer: A. This patient has reversible ischemia on the stress test: exactly the person who needs angiography. If the presentation of anginal chest pain is 100% specific for coronary disease, there is not much point in doing a stress test. Even if it comes back negative, the patient likely has coronary disease. The stress test is precisely for when you are not sure of etiology. When isotope uptake is normal at rest and decreases on exercise, you have found the person who can benefit from revascularization. You cannot determine what type of revascularization until after you know the anatomy. If there is no reversibility in ischemia between rest and exercise, there is little to be gained from revascularization. Irreversible (fixed) defects mean dead (infarcted) myocardium. There is not much point in revascularizing dead tissue; it is too late. There is a point in revascularizing reversible defects. The tissue can be saved, and you can prevent infarction. Reversible perfusion defects need catheterization. Catheterization indicates which patients get bypass versus angioplasty versus medications alone.

Adenosine and dipyridamole increase flow in normal arteries.

Before administering a dipyridamole stress test, stop caffeine.

TIP: The 2 methods that can detect ischemia in terms of using nuclear isotopes or echo are essentially equal in terms of sensitivity and specificity.

Exercise thallium = Exercise echo

Dipyridamole thallium = Dobutamine echo

Coronary Angiography

Angiography is used to detect the anatomic location of coronary artery disease. Angiography is predominantly a test to detect the presence of narrowing that is best managed with surgery, angioplasty, or other methods of revascularization. Sometimes angiography is used if noninvasive tests such as EKG or stress testing are equivocal. Angiography is the most accurate method of detecting coronary artery disease.

Angiography determines bypass surgery vs. angioplasty.

Stenosis (narrowing) <50% of the diameter is insignificant. Surgically correctable disease generally begins with ≥70% stenosis.

Figure 2.3 Chest Pain Diagnosis Algorithm

Holter Monitoring

The Holter monitor is a continuous ambulatory EKG monitor that records the rhythm; it is usually used for 24–48 hours but may be continued for months. Holter monitoring mainly detects rhythm disorders including atrial fibrillation (A-fib), flutter, ectopy such as premature beats, or ventricular tachycardia. Holter monitor does not detect ischemia and is not accurate for evaluating the ST segment. This can be implanted as a loop recorder under the skin for months.

Holter monitoring is used only for rhythm evaluation.

A 48-year-old woman comes to the office with chest pain that has been occurring over the last several weeks. The pain is not reliably related to exertion. She is comfortable now. The location of the pain is retrosternal. She has no hypertension, and the EKG is normal. What is the most appropriate next step in management?

CK-MB

Troponin

Echocardiogram

Exercise tolerance testing

Angiography

CT angiography

Cardiac MRI

Holter monitor

Answer: D. Enzymes are to evaluate acute coronary syndromes. Serial troponin measurements are done prior to stress test. Echocardiography is to evaluate valve function, wall motion, and ejection fraction. Exercise tolerance testing is to evaluate stable patients with chest pain whose diagnoses are not clear. ETT is not used in acute coronary syndrome cases in which the patient is currently having pain and the diagnosis is already clear. Also, don’t put patients on a treadmill to exercise if they are currently having chest pain.

Treatment

USMLE Step 2 CK is most concerned that you know the medications that will lower mortality. For a patient with chronic angina (not an acute coronary syndrome), the therapeutic options are easier. There are only a few right choices:

Aspirin

Beta blockers

Statins

USMLE Step 2 CK, like most board examinations, will not test dosing, although the route of administration is important to know. Knowing that nitroglycerin can be used either orally or by transdermal patch in chronic angina is important, but knowing the specific dose is not. Knowing that sublingual, paste, and intravenous forms of nitroglycerin are used in acute coronary syndromes, but not in chronic angina, is important. Knowing how much paste is not important.

Antiplatelet Therapy

Stable CAD patients and those without a stent only need aspirin.

Ticagrelor is an antiplatelet medication added to aspirin. It is an alternative to prasugrel or clopidogrel.

ACE Inhibitors/Angiotensin Receptor Blockers/ARNIs

Low ejection fraction/systolic dysfunction (best mortality benefit)

Cough is the most common adverse effect of ACE inhibitors, occurring in up to 7% of patients.

Angiotensin receptor blocker (ARB) combined with the neprilysin inhibitor sacubitril (ARNI) are coequal with ACE inhibitors for CHF. ARNIs can falsely elevate the brain natriuretic peptide (BNP) level.

Beta Blockers

Beta blockers are the first-line therapy in patients with stable angina. They work by decreasing myocardial contractility, heart rate, and O2 demand. Decreased heart rate prolongs diastole, which increases coronary perfusion. All beta blockers are equally effective in exertional angina; however, due to their side effects, nonselective beta blockers are rarely used.

The beta-1 specific agent metoprolol is the #1 beta blocker for coronary disease.

Lipid Management: Statins

What is clear on lipid management? Everyone will agree that with CAD, the goal of LDL should be 70 mg/dL or lower. In primary prevention, start a statin if the 10-year risk of CAD is >7.5%. High-intensity statin means atorvastatin or rosuvastatin.

TIP: Statins (HMG CoA reductase inhibitors)

Use in CAD with any level of LDL

The goal is an LDL of 70 mg/dL or lower

There is no LDL level at which to start statin medications in those with coronary artery disease, stroke, or peripheral artery disease. Everyone with vascular disease should be on a statin.

TIP: The following are CAD equivalents, and statins should be used in all of these:

Peripheral artery disease (PAD)

Carotid disease

Aortic disease (the aortic artery, not the valve)

Stroke

MI

Clear indications for the use of statins:

Acute coronary syndrome

MI or stenting

Any arterial disease

10-year risk of CAD >7.5%

It is clear that only statins are associated with a definite mortality benefit in the management of hyperlipidemia. If there is intolerance of a specific statin, switch to another statin.

Which of the following is the most common adverse effect of statins?

Rhabdomyolysis

Liver dysfunction

Renal failure

Encephalopathy

Hyperkalemia

Answer: B. At least 2–3% of patients taking statin medications will develop elevation of transaminases to the level where you will need to discontinue the medication. Myositis, elevation of CPK levels, or rhabdomyolysis will occur in less than 0.1% of patients. It is very rare to have to stop statins because of myositis. There is no recommendation to routinely test all patients for CPK levels in the absence of symptoms. On the other hand, all patients started on statins should have their AST and ALT tested as a matter of routine monitoring, even if no symptoms are present.

Other Lipid-Lowering Therapies

Niacin, gemfibrozil, and ezetimibe all have beneficial effects on lipid profiles. However, none of them is the best initial therapy because none of them has the clear mortality benefit in CAD that statins provide. Statins have an antioxidant effect on the endothelial lining of the coronary arteries that gives a benefit that transcends simply lowering the LDL number. When statin alone fails to achieve the LDL goal, add ezetimibe.

Ezetimibe: This agent definitely lowers LDL level. However, LDL levels are an imperfect marker of benefit with cholesterol-lowering therapies.

Niacin: Associated with glucose intolerance, elevation of uric acid level, and an uncomfortable itchiness or flushing from a transient release of prostaglandins. Although niacin has the best effect on raising HDL, there is no significant mortality benefit.

The only niacin question will be on its adverse effect: flushing from elevated prostaglandins.

Gemfibrozil: Fibric acid derivatives lower triglyceride levels somewhat more than statins; however, the benefit of lowering triglycerides alone has not proven to be as useful as the straightforward mortality benefit of statins. Use caution in combining fibrates with statins because of an increased risk of myositis.

PCSK9 Inhibitors

Evolocumab and alirocumab inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 inhibitors (injectable medications) do the following:

Increase LDL clearance from the blood by blocking the breakdown of LDL receptors in the liver

Decrease elevated LDL significantly in familial hypercholesterolemia

Increase hepatic clearance of LDL massively, but do not lower mortality

With severe hyperlipidemia, if LDL is not controlled with a statin and ezetimibe at maximum doses, try a PCSK9 inhibitor.

Check AST and ALT when using statins.

Calcium Channel Blockers

Dihydropyridine calcium channel blockers (CCBs) such as nifedipine, nitrendipine, nicardipine, and nimodipine may actually increase mortality in patients with CAD because of their effect in raising heart rates. The best example of an increased heart rate is the reflex tachycardia developing from the use of nifedipine. This is probably the best explanation for the failure of the CCBs to decrease mortality.

None of the calcium channel blockers have been shown to lower mortality in CAD.

Bottom line: Do not routinely use CCBs in CAD. Use CCBs (verapamil/diltiazem) in CAD only with:

Severe asthma precluding the use of beta blockers

Prinzmetal variant angina

Cocaine-induced chest pain (beta blockers are safe)

Inability to control pain with maximum medical therapy

Adverse effects of CCBs:

Edema

Constipation

Heart block (rare)

When studying medications, you must know the clear adverse effects. These USMLE Step 2 CK questions do not change over time.

Ranolazine

Ranolazine is a sodium channel–blocking medication that treats angina. Ranolazine is added to those who still have pain despite aspirin, beta blockers, nitrates, and calcium blockers. It does not have a clear mortality benefit.

Revascularization

Angiography is indispensable in evaluating a patient for the possibility of revascularization, which is either coronary bypass surgery or angioplasty. Symptoms alone cannot tell the number of vessels involved, what vessels are involved, or the degree or percentage of stenosis.

Coronary artery bypass grafting (CABG) lowers mortality only in a few specific circumstances with manifestations of very severe disease such as:

Three vessels with at least 70% stenosis in each vessel

Left main coronary artery occlusion

Two-vessel disease in a patient with diabetes

Persistent symptoms despite maximal medical therapy

Long-term mortality benefit from CABG is greater with the most severe disease such as left ventricular dysfunction. The immediate operative mortality may be greater in patients with an ejection fraction (EF) <35%, but in the long term, those with 3-vessel disease have improved survival with coronary bypass surgery if they survive the procedure.

Internal mammary artery grafts last on average for 10 years before they occlude, whereas saphenous vein grafts remain patent reliably for only 5 years. Half of vein grafts are patent at 10 years.

Percutaneous coronary intervention (PCI) is also referred to as angioplasty. The term intervention is more precise, because there are other interventions besides angioplasty. PCI is unquestionably the best therapy in acute coronary syndromes, particularly those with ST segment elevation. Maximal medical therapy with aspirin, beta blockers, ACEIs/ARBs, and statins has proven to have equal or even superior benefit compared to PCI in stable CAD. PCI is more definitive in terms of decreasing dependence on medication and decreasing frequency of painful angina episodes.

PCI is the best in acute coronary syndromes, particularly with ST segment elevation. PCI does not provide clear mortality benefit for stable patients.

Dipyridamole is never the right choice for coronary artery disease. 

Acute Coronary Syndromes

It is impossible to determine the precise etiology of acute coronary syndromes (ACS) from history and physical examination alone. The risk factors (e.g., hypertension, diabetes mellitus, tobacco) are the same as those described previously for CAD.

A 70-year-old woman comes to the ED with crushing substernal chest pain for the last hour. The pain radiates to her left arm and is associated with anxiety, diaphoresis, and nausea. She describes the pain as sore and dull, and she clenches her fist in front of her chest. She has a history of hypertension. Which of the following is most likely to be found?

Decrease of >10 mm Hg in blood pressure on inhalation

Increase in jugular venous pressure on inhalation

Triphasic scratchy sound on auscultation

Continuous machinery murmur

S4 gallop

Point of maximal impulse displaced toward the axilla

Answer: E. Acute coronary syndromes are associated with an S4 gallop because of ischemia leading to noncompliance of the left ventricle. The S4 gallop is the sound of atrial systole as blood is ejected from the atrium into a stiff ventricle. A decrease of blood pressure >10 mm Hg on inspiration is a pulsus paradoxus and is associated with cardiac tamponade.

An increase in jugulovenous pressure on inhalation is the Kussmaul sign and is most often associated with constrictive pericarditis or restrictive cardiomyopathy. A triphasic scratchy sound is a pericardial friction rub. Although pericarditis can occur as a complication of myocardial infarction (Dressler syndrome), this would not occur for several days after an MI and is much rarer than simple ventricular ischemia.

Figure 2.4 Acute Coronary Syndromes Diagnosis Algorithm

TIP: A continuous machinery murmur is what would be found with a patent ductus arteriosus.

A displaced point of maximal impulse (PMI) is characteristic of left ventricular hypertrophy (LVH) as well as dilated cardiomyopathy. A displaced PMI is an anatomic abnormality that could not possibly occur with an acute coronary syndrome.

There are no specific physical findings to allow you to answer a most likely diagnosis question in terms of ST elevation or depression without an EKG.

A 70-year-old woman comes to the ED with crushing substernal chest pain for the last hour. Which of the following EKG findings would be associated with the worst prognosis?

ST elevation in leads II, III, aVF

PR interval >200 milliseconds

ST elevation in leads V2–V4

Frequent premature ventricular complexes (PVCs)

ST depression in leads V1 and V2

Right bundle branch block (RBBB)

Answer: C. Leads V2 to V4 correspond to the anterior wall of the left ventricle. ST segment elevation most often signifies an acute myocardial infarction. ST elevation in leads II, III, and aVF is also consistent with an acute myocardial infarction, but of the inferior wall. Untreated, the mortality associated with an IWMI is <5% at 1 year after the event. With an AWMI, mortality untreated is closer to 30–40%. PR interval >200 milliseconds is first-degree atrioventricular (AV) block. First-degree AV block has little pathologic potential and, when isolated, requires no additional therapy. Ectopy such as PVCs and atrial premature complexes (APCs) are associated with the later development of more severe arrhythmias, but no additional therapy is needed for them if magnesium and potassium levels are normal. PVCs do not require any changes in management. ST depressions in leads V1 and V2 are suggestive of a posterior wall myocardial infarction. These leads are read in the opposite direction of the rest of the leads. In other words, ST depression in leads V1 and V2 would be like ST elevation elsewhere—an acute infarction. Infarctions of the posterior wall are associated with a very low mortality, and again, there is no additional therapy to give because of it. Right bundle branch block (RBBB) is benign compared to a new left bundle branch block (LBBB).

Do not walk into your USMLE Step 2 CK exam without knowing when you will expect each of the cardiac physical findings described here.

PVCs should not be treated, even when associated with an acute infarction. Treatment of PVCs only worsens outcome.

A 70-year-old woman comes to the ED with crushing substernal chest pain for the last hour. EKG shows ST segment elevation in V2 to V4. What is the most appropriate next step in management?

CK-MB level

Oxygen

Nitroglycerin sublingual

Aspirin

Thrombolytics

Metoprolol

Atorvastatin

Angioplasty

Consult cardiology

Transfer patient to ICU

Troponin level

Morphine

Angiography

Clopidogrel

Answer: D. Aspirin lowers mortality with ACS, and it is critical to administer rapidly. With only 1 hour since the onset of pain, neither the CK-MB nor the troponin would yet be elevated. Morphine, oxygen, and nitroglycerin do not lower mortality, so they are not as important as aspirin. Aspirin should be given simultaneously with activating the catheterization lab. Either clopidogrel, prasugrel, or ticagrelor is indicated in any patient with an acute MI. Transfer the patient to the ICU, but always initiate therapy and testing before doing so. Starting proper care first is critical. Thrombolytics or angioplasty should be done (and quickly), but aspirin should be given first. Aspirin and a second antiplatelet drug are then followed with another form of acute revascularization.

All MIs get 2 antiplatelet drugs.

Oxygen does not help nonhypoxic patients.

TIP: On the USMLE Step 2 CK exam, consultation is almost never the correct choice. Do everything yourself.

One of the most critical points of preparation is knowing the order in which to do things. It is not enough to know which tests and treatments must be done. You must be able to prioritize what is first.

A 70-year-old woman comes to the ED with crushing substernal chest pain for the last hour. An EKG shows ST segment elevation in V2 to V4. Aspirin and clopidogrel have been given. What is the most appropriate next step in management?

CK-MB level

Oxygen

Nitroglycerin sublingual

Morphine

Thrombolytics

Metoprolol

Atorvastatin

Angioplasty

Troponin level

Lisinopril

Answer: H. Angioplasty is associated with the greatest mortality benefit of all the steps listed in this question. All of the answer choices are partially correct in that they should all be done for the patient. Nitrates should be given to the patient immediately, but they do not clearly lower mortality. Enzyme tests should be done, but within the first 4 hours of the onset of chest pain they will certainly be normal. Even if they are elevated, CK-MB and troponin levels would not alter the management. Beta blockers are associated with a