The Ultimate and Complete 2025 High-Yield Clinical
COMSAE 115 Study Guide, Covering Osteopathic Medical
Knowledge Integration, High-Yield Clinical Reasoning
Strategies, Pathophysiology and Disease Correlation,
Cardiology Pulmonology and Neurology Core Concepts,
Gastrointestinal and Renal System Review, Endocrine and
Metabolic Disorders, Musculoskeletal and OMM
Integration Principles, Infectious Disease and
Pharmacology Essentials, Preventive Medicine and Public
Health Concepts, Diagnostic Reasoning and Test
Interpretation Skills, COMSAE 115 Exam Blueprint
Breakdown, Rapid Recall High-Yield Facts and Clinical
Pearls, Practice Questions with Verified Answers and
Detailed Rationales, Real Clinical Vignette Case
Scenarios, Step-by-Step NBOME-Style Problem Solving,
and Proven Strategies to Successfully Maximize COMSAE
115 Performance and Prepare for COMLEX-USA Success
Question 1: 65yo M w/ HTN has sudden tearing chest pain to back. BP 190/110 R arm, 160/90
L arm. CXR: widened mediastinum. Dx? A. Acute MI B. PE C. Aortic dissection D. Pneumothorax
CORRECT ANSWER: C. Aortic dissection Rationale: Tearing chest pain, asymmetric BP, and
widened mediastinum indicate aortic dissection. MI causes crushing pain; PE causes pleuritic
pain; pneumothorax causes absent breath sounds.
Question 2: 55yo M w/ smoking hx presents w/ crushing substernal chest pain radiating to
left arm. ECG shows ST elevations in II, III, aVF. Occluded artery? A. LAD B. RCA C. LCx D. PDA
CORRECT ANSWER: B. RCA Rationale: ST elevations in II, III, aVF indicate an inferior MI, typically
caused by RCA occlusion. LAD occlusion affects V1-V4; LCx affects I, aVL, V5-V6.
Question 3: 22yo F presents w/ sharp, pleuritic chest pain that improves when leaning
forward. ECG shows diffuse ST elevations and PR depressions. Dx? A. Acute MI B. Pericarditis
C. PE D. Aortic dissection CORRECT ANSWER: B. Pericarditis Rationale: Pleuritic chest pain
improving with leaning forward and diffuse ST elevations/PR depressions are classic for acute
pericarditis. MI shows localized ST elevations; PE shows S1Q3T3.
Question 4: 40yo F w/ SLE presents w/ hypotension, JVD, and muffled heart sounds. Pulsus
paradoxus is present. Dx? A. Cardiac tamponade B. Constrictive pericarditis C. Tension
pneumothorax D. Acute MI CORRECT ANSWER: A. Cardiac tamponade Rationale: Beck's triad
,(hypotension, JVD, muffled heart sounds) and pulsus paradoxus indicate cardiac tamponade.
Constrictive pericarditis presents with chronic right heart failure signs.
Question 5: 70yo M w/ hx of ischemic cardiomyopathy presents w/ progressive dyspnea,
orthopnea, and bilateral lower extremity edema. Echo shows EF of 25%. Dx? A. Systolic heart
failure B. Diastolic heart failure C. Cor pulmonale D. Constrictive pericarditis CORRECT ANSWER:
A. Systolic heart failure Rationale: Reduced EF (<40%) with volume overload indicates systolic
heart failure (HFrEF). Diastolic heart failure has preserved EF (>50%) with impaired relaxation.
Question 6: 68yo F w/ HTN presents w/ dyspnea on exertion. Echo shows EF 60% but severe
LV hypertrophy and diastolic dysfunction. Dx? A. Systolic heart failure B. Diastolic heart failure
C. Cor pulmonale D. Hypertrophic cardiomyopathy CORRECT ANSWER: B. Diastolic heart
failure Rationale: Preserved EF with diastolic dysfunction and LV hypertrophy indicates diastolic
heart failure (HFpEF). Systolic HF has reduced EF.
Question 7: 75yo M w/ irregularly irregular pulse and no P waves on ECG. HR is 130 bpm.
Most appropriate initial rate control? A. Amiodarone B. Metoprolol C. Adenosine D. Lidocaine
CORRECT ANSWER: B. Metoprolol Rationale: Atrial fibrillation with RVR requires rate control
with beta-blockers or non-dihydropyridine CCBs. Amiodarone is for rhythm control; adenosine
is for SVT.
Question 8: 25yo F presents w/ sudden palpitations. ECG shows narrow complex tachycardia
at 180 bpm with no visible P waves. Vagal maneuvers fail. Next step? A. Amiodarone B.
Metoprolol C. Adenosine D. Defibrillation CORRECT ANSWER: C. Adenosine Rationale: SVT is
treated initially with vagal maneuvers, followed by IV adenosine. Beta-blockers are second-line;
defibrillation is for unstable patients or V-fib.
Question 9: 60yo M post-MI presents w/ wide complex tachycardia at 200 bpm and
hypotension. Immediate treatment? A. Amiodarone B. Adenosine C. Synchronized
cardioversion D. Defibrillation CORRECT ANSWER: C. Synchronized cardioversion Rationale:
Unstable ventricular tachycardia requires immediate synchronized cardioversion. Defibrillation
is for pulseless VT or V-fib; amiodarone is for stable VT.
Question 10: 30yo F w/ eating disorder presents w/ syncope. ECG shows prolonged QT
interval. She is started on an antibiotic that worsens this. Which antibiotic? A. Amoxicillin B.
Azithromycin C. Ciprofloxacin D. Metronidazole CORRECT ANSWER: B. Azithromycin Rationale:
Macrolides (azithromycin) prolong the QT interval, increasing the risk of Torsades de pointes.
Fluoroquinolones also prolong QT, but azithromycin is a classic culprit.
Question 11: 20yo M presents w/ syncope during basketball. ECG shows short PR interval and
delta wave. Dx? A. Brugada syndrome B. Long QT syndrome C. Wolff-Parkinson-White
syndrome D. Hypertrophic cardiomyopathy CORRECT ANSWER: C. Wolff-Parkinson-White
syndrome Rationale: Short PR interval and delta wave on ECG are pathognomonic for WPW
syndrome, caused by an accessory pathway (Bundle of Kent).
, Question 12: 35yo F w/ hx of rheumatic fever presents w/ dyspnea and hemoptysis.
Auscultation reveals a loud S1 and opening snap followed by a diastolic rumble. Dx? A. Mitral
stenosis B. Mitral regurgitation C. Aortic stenosis D. Aortic regurgitation CORRECT ANSWER: A.
Mitral stenosis Rationale: Loud S1, opening snap, and diastolic rumble are classic for mitral
stenosis, often a sequela of rheumatic fever.
Question 13: 65yo M presents w/ fatigue and dyspnea. Auscultation reveals a holosystolic
murmur at the apex radiating to the axilla. Dx? A. Mitral stenosis B. Mitral regurgitation C.
Aortic stenosis D. Aortic regurgitation CORRECT ANSWER: B. Mitral regurgitation Rationale:
Holosystolic murmur at the apex radiating to the axilla is classic for mitral regurgitation.
Question 14: 70yo M presents w/ syncope and angina. Auscultation reveals a crescendo-
decrescendo systolic murmur at the right upper sternal border radiating to the carotids. Dx?
A. Mitral stenosis B. Mitral regurgitation C. Aortic stenosis D. Aortic regurgitation CORRECT
ANSWER: C. Aortic stenosis Rationale: Crescendo-decrescendo systolic murmur at the right
upper sternal border radiating to the carotids is classic for aortic stenosis.
Question 15: 50yo M presents w/ bounding pulses and head bobbing. Auscultation reveals an
early diastolic decrescendo murmur at the left sternal border. Dx? A. Mitral stenosis B. Mitral
regurgitation C. Aortic stenosis D. Aortic regurgitation CORRECT ANSWER: D. Aortic
regurgitation Rationale: Early diastolic decrescendo murmur with bounding pulses (Water-
hammer pulse) and head bobbing (De Musset's sign) indicates aortic regurgitation.
Question 16: 22yo M collapses during exercise. Echo shows asymmetric septal hypertrophy.
Murmur increases with Valsalva. Dx? A. Dilated cardiomyopathy B. Restrictive cardiomyopathy
C. Hypertrophic cardiomyopathy D. Arrhythmogenic right ventricular cardiomyopathy CORRECT
ANSWER: C. Hypertrophic cardiomyopathy Rationale: Asymmetric septal hypertrophy and a
murmur that increases with Valsalva (decreased preload) are classic for hypertrophic
cardiomyopathy (HCM).
Question 17: 25yo F w/ hx of asthma presents w/ wheezing and shortness of breath.
Spirometry shows FEV1/FVC < 70% that improves with albuterol. Dx? A. COPD B. Asthma C.
Restrictive lung disease D. Pulmonary fibrosis CORRECT ANSWER: B. Asthma Rationale:
Obstructive pattern (FEV1/FVC < 70%) that is reversible with bronchodilators indicates asthma.
COPD is largely irreversible.
Question 18: 65yo M w/ 40 pack-year smoking hx presents w/ chronic cough and dyspnea.
Spirometry shows FEV1/FVC < 70% with no significant reversibility. Dx? A. Asthma B. COPD C.
Restrictive lung disease D. Interstitial lung disease CORRECT ANSWER: B. COPD Rationale:
Irreversible obstructive pattern (FEV1/FVC < 70%) in a smoker indicates COPD (chronic
bronchitis and/or emphysema).
Question 19: 70yo M presents w/ high fever, productive cough with rust-colored sputum, and
lobar consolidation on CXR. Gram stain shows Gram-positive diplococci. Dx? A. Mycoplasma
COMSAE 115 Study Guide, Covering Osteopathic Medical
Knowledge Integration, High-Yield Clinical Reasoning
Strategies, Pathophysiology and Disease Correlation,
Cardiology Pulmonology and Neurology Core Concepts,
Gastrointestinal and Renal System Review, Endocrine and
Metabolic Disorders, Musculoskeletal and OMM
Integration Principles, Infectious Disease and
Pharmacology Essentials, Preventive Medicine and Public
Health Concepts, Diagnostic Reasoning and Test
Interpretation Skills, COMSAE 115 Exam Blueprint
Breakdown, Rapid Recall High-Yield Facts and Clinical
Pearls, Practice Questions with Verified Answers and
Detailed Rationales, Real Clinical Vignette Case
Scenarios, Step-by-Step NBOME-Style Problem Solving,
and Proven Strategies to Successfully Maximize COMSAE
115 Performance and Prepare for COMLEX-USA Success
Question 1: 65yo M w/ HTN has sudden tearing chest pain to back. BP 190/110 R arm, 160/90
L arm. CXR: widened mediastinum. Dx? A. Acute MI B. PE C. Aortic dissection D. Pneumothorax
CORRECT ANSWER: C. Aortic dissection Rationale: Tearing chest pain, asymmetric BP, and
widened mediastinum indicate aortic dissection. MI causes crushing pain; PE causes pleuritic
pain; pneumothorax causes absent breath sounds.
Question 2: 55yo M w/ smoking hx presents w/ crushing substernal chest pain radiating to
left arm. ECG shows ST elevations in II, III, aVF. Occluded artery? A. LAD B. RCA C. LCx D. PDA
CORRECT ANSWER: B. RCA Rationale: ST elevations in II, III, aVF indicate an inferior MI, typically
caused by RCA occlusion. LAD occlusion affects V1-V4; LCx affects I, aVL, V5-V6.
Question 3: 22yo F presents w/ sharp, pleuritic chest pain that improves when leaning
forward. ECG shows diffuse ST elevations and PR depressions. Dx? A. Acute MI B. Pericarditis
C. PE D. Aortic dissection CORRECT ANSWER: B. Pericarditis Rationale: Pleuritic chest pain
improving with leaning forward and diffuse ST elevations/PR depressions are classic for acute
pericarditis. MI shows localized ST elevations; PE shows S1Q3T3.
Question 4: 40yo F w/ SLE presents w/ hypotension, JVD, and muffled heart sounds. Pulsus
paradoxus is present. Dx? A. Cardiac tamponade B. Constrictive pericarditis C. Tension
pneumothorax D. Acute MI CORRECT ANSWER: A. Cardiac tamponade Rationale: Beck's triad
,(hypotension, JVD, muffled heart sounds) and pulsus paradoxus indicate cardiac tamponade.
Constrictive pericarditis presents with chronic right heart failure signs.
Question 5: 70yo M w/ hx of ischemic cardiomyopathy presents w/ progressive dyspnea,
orthopnea, and bilateral lower extremity edema. Echo shows EF of 25%. Dx? A. Systolic heart
failure B. Diastolic heart failure C. Cor pulmonale D. Constrictive pericarditis CORRECT ANSWER:
A. Systolic heart failure Rationale: Reduced EF (<40%) with volume overload indicates systolic
heart failure (HFrEF). Diastolic heart failure has preserved EF (>50%) with impaired relaxation.
Question 6: 68yo F w/ HTN presents w/ dyspnea on exertion. Echo shows EF 60% but severe
LV hypertrophy and diastolic dysfunction. Dx? A. Systolic heart failure B. Diastolic heart failure
C. Cor pulmonale D. Hypertrophic cardiomyopathy CORRECT ANSWER: B. Diastolic heart
failure Rationale: Preserved EF with diastolic dysfunction and LV hypertrophy indicates diastolic
heart failure (HFpEF). Systolic HF has reduced EF.
Question 7: 75yo M w/ irregularly irregular pulse and no P waves on ECG. HR is 130 bpm.
Most appropriate initial rate control? A. Amiodarone B. Metoprolol C. Adenosine D. Lidocaine
CORRECT ANSWER: B. Metoprolol Rationale: Atrial fibrillation with RVR requires rate control
with beta-blockers or non-dihydropyridine CCBs. Amiodarone is for rhythm control; adenosine
is for SVT.
Question 8: 25yo F presents w/ sudden palpitations. ECG shows narrow complex tachycardia
at 180 bpm with no visible P waves. Vagal maneuvers fail. Next step? A. Amiodarone B.
Metoprolol C. Adenosine D. Defibrillation CORRECT ANSWER: C. Adenosine Rationale: SVT is
treated initially with vagal maneuvers, followed by IV adenosine. Beta-blockers are second-line;
defibrillation is for unstable patients or V-fib.
Question 9: 60yo M post-MI presents w/ wide complex tachycardia at 200 bpm and
hypotension. Immediate treatment? A. Amiodarone B. Adenosine C. Synchronized
cardioversion D. Defibrillation CORRECT ANSWER: C. Synchronized cardioversion Rationale:
Unstable ventricular tachycardia requires immediate synchronized cardioversion. Defibrillation
is for pulseless VT or V-fib; amiodarone is for stable VT.
Question 10: 30yo F w/ eating disorder presents w/ syncope. ECG shows prolonged QT
interval. She is started on an antibiotic that worsens this. Which antibiotic? A. Amoxicillin B.
Azithromycin C. Ciprofloxacin D. Metronidazole CORRECT ANSWER: B. Azithromycin Rationale:
Macrolides (azithromycin) prolong the QT interval, increasing the risk of Torsades de pointes.
Fluoroquinolones also prolong QT, but azithromycin is a classic culprit.
Question 11: 20yo M presents w/ syncope during basketball. ECG shows short PR interval and
delta wave. Dx? A. Brugada syndrome B. Long QT syndrome C. Wolff-Parkinson-White
syndrome D. Hypertrophic cardiomyopathy CORRECT ANSWER: C. Wolff-Parkinson-White
syndrome Rationale: Short PR interval and delta wave on ECG are pathognomonic for WPW
syndrome, caused by an accessory pathway (Bundle of Kent).
, Question 12: 35yo F w/ hx of rheumatic fever presents w/ dyspnea and hemoptysis.
Auscultation reveals a loud S1 and opening snap followed by a diastolic rumble. Dx? A. Mitral
stenosis B. Mitral regurgitation C. Aortic stenosis D. Aortic regurgitation CORRECT ANSWER: A.
Mitral stenosis Rationale: Loud S1, opening snap, and diastolic rumble are classic for mitral
stenosis, often a sequela of rheumatic fever.
Question 13: 65yo M presents w/ fatigue and dyspnea. Auscultation reveals a holosystolic
murmur at the apex radiating to the axilla. Dx? A. Mitral stenosis B. Mitral regurgitation C.
Aortic stenosis D. Aortic regurgitation CORRECT ANSWER: B. Mitral regurgitation Rationale:
Holosystolic murmur at the apex radiating to the axilla is classic for mitral regurgitation.
Question 14: 70yo M presents w/ syncope and angina. Auscultation reveals a crescendo-
decrescendo systolic murmur at the right upper sternal border radiating to the carotids. Dx?
A. Mitral stenosis B. Mitral regurgitation C. Aortic stenosis D. Aortic regurgitation CORRECT
ANSWER: C. Aortic stenosis Rationale: Crescendo-decrescendo systolic murmur at the right
upper sternal border radiating to the carotids is classic for aortic stenosis.
Question 15: 50yo M presents w/ bounding pulses and head bobbing. Auscultation reveals an
early diastolic decrescendo murmur at the left sternal border. Dx? A. Mitral stenosis B. Mitral
regurgitation C. Aortic stenosis D. Aortic regurgitation CORRECT ANSWER: D. Aortic
regurgitation Rationale: Early diastolic decrescendo murmur with bounding pulses (Water-
hammer pulse) and head bobbing (De Musset's sign) indicates aortic regurgitation.
Question 16: 22yo M collapses during exercise. Echo shows asymmetric septal hypertrophy.
Murmur increases with Valsalva. Dx? A. Dilated cardiomyopathy B. Restrictive cardiomyopathy
C. Hypertrophic cardiomyopathy D. Arrhythmogenic right ventricular cardiomyopathy CORRECT
ANSWER: C. Hypertrophic cardiomyopathy Rationale: Asymmetric septal hypertrophy and a
murmur that increases with Valsalva (decreased preload) are classic for hypertrophic
cardiomyopathy (HCM).
Question 17: 25yo F w/ hx of asthma presents w/ wheezing and shortness of breath.
Spirometry shows FEV1/FVC < 70% that improves with albuterol. Dx? A. COPD B. Asthma C.
Restrictive lung disease D. Pulmonary fibrosis CORRECT ANSWER: B. Asthma Rationale:
Obstructive pattern (FEV1/FVC < 70%) that is reversible with bronchodilators indicates asthma.
COPD is largely irreversible.
Question 18: 65yo M w/ 40 pack-year smoking hx presents w/ chronic cough and dyspnea.
Spirometry shows FEV1/FVC < 70% with no significant reversibility. Dx? A. Asthma B. COPD C.
Restrictive lung disease D. Interstitial lung disease CORRECT ANSWER: B. COPD Rationale:
Irreversible obstructive pattern (FEV1/FVC < 70%) in a smoker indicates COPD (chronic
bronchitis and/or emphysema).
Question 19: 70yo M presents w/ high fever, productive cough with rust-colored sputum, and
lobar consolidation on CXR. Gram stain shows Gram-positive diplococci. Dx? A. Mycoplasma
