A 25-year-old man comes to the office due to shortness of breath. He states that even moderate exertion forces him to stop to catch his breath. The patient has no family history of sudden cardiac death. He does not use tobacco or illicit drugs. On examination, the patient has a faint systolic murmur at the left sternal border in the supine position that increases to 3/6 in intensity with Valsalva maneuver. Echocardiography shows interventricular septal hypertrophy and increased left ventricular mass. The patient is started on high-dose beta blocker therapy. On follow-up 2 weeks later, he reports significant improvement in his shortness of breath. Physical examination reveals no murmurs supine or with Valsalva. Which of the following best accounts for improvement of this patient's symptoms?

Question

A 25-year-old man comes to the office due to shortness of breath.  He states that even moderate exertion forces him to stop to catch his breath.  The patient has no family history of sudden cardiac death.  He does not use tobacco or illicit drugs.  On examination, the patient has a faint systolic murmur at the left sternal border in the supine position that increases to 3/6 in intensity with Valsalva maneuver.  Echocardiography shows interventricular septal hypertrophy and increased left ventricular mass.  The patient is started on high-dose beta blocker therapy.  On follow-up 2 weeks later, he reports significant improvement in his shortness of breath.  Physical examination reveals no murmurs supine or with Valsalva.  Which of the following best accounts for improvement of this patient's symptoms?

Quizplus · Accepted Answer

This patient's echocardiogram shows increased left ventricular (LV) mass with predominant interventricular septal hypertrophy, which are classic findings for hypertrophic cardiomyopathy (HCM). Many patients with HCM have LV outflow tract obstruction that can lead to symptoms of poor cardiac output (eg, dyspnea, syncope). The outflow tract obstruction worsens with decreased LV blood volume (as can occur during exercise due to decreased LV filling time and increased LV contractility); on physical examination, this effect is evidenced by a systolic murmur that increases in intensity with maneuvers that decrease LV blood volume (eg, Valsalva strain phase, abrupt standing). In patients with HCM and symptomatic LV outflow tract obstruction, beta blockers (eg, metoprolol, nadolol) improve symptoms mostly via an increase in LV volume that reduces LV outflow tract obstruction. This occurs via the following 2 mechanisms: Beta blockers reduce heart rate, which lengthens diastolic filling time to increase LV end-diastolic volume (ie, preload) Beta blockers reduce LV contractility, which decreases the amount of blood ejected during ventricular systole (ie, increased end-systolic volume) Nondihydropyridine calcium channel blockers (eg, verapamil) have similar effects and can be used in patients with a contraindication to beta blockers or as additional therapy for persistent symptoms. (Choice A) Some patients with HCM may experience anginal symptoms due to inadequate blood supply to the increased myocardial mass. Beta blockers may help alleviate these symptoms by decreasing LV wall stress to reduce myocardial oxygen demand and improve the coronary artery perfusion gradient; however, they have minimal dilatory effect on the coronary arteries. (Choice B) By increasing the cross-sectional area of the LV outflow tract, beta blockers tend to decrease flow velocity (flow velocity = volumetric flow rate / cross-sectional area). Consequently, the intensity of the HCM murmur is also decreased. (Choice D) Over time, beta blockers may reduce the compensatory LV hypertrophy that can occur in HCM due to prolonged contraction against the outflow tract obstruction (similar to aortic stenosis); however, this effect would not be evident within 2 weeks. (Choice E) Beta blockers increase LV preload. Medications that reduce LV preload (eg, nitrates, diuretics) can worsen LV outflow tract obstruction and should be avoided in patients with HCM. Educational objective: Many patients with hypertrophic cardiomyopathy have exercise intolerance due to left ventricular (LV) outflow tract obstruction. This outflow obstruction is worsened by decreased LV blood volume. Beta blockers decrease heart rate and LV contractility to increase LV blood volume, reduce LV outflow tract obstruction, and improve symptoms.

A 25-Year-Old Man Comes to the Office Due to Shortness