A 68-year-old man comes to the office due to exertional shortness of breath and fatigue, which have progressed over the past year. The patient has a history of hypertension, but medical history is otherwise unremarkable. He is a lifetime nonsmoker. His father died of a "heart attack" at age 70. Blood pressure is 144/74 mm Hg, and pulse is 72/min and regular. Cardiac auscultation reveals a 3/6 ejection-type, late-peaking systolic murmur and a barely audible S2. The murmur diminishes in intensity during the straining phase of the Valsalva maneuver. Which of the following processes underlies this patient's current condition?

Question

A 68-year-old man comes to the office due to exertional shortness of breath and fatigue, which have progressed over the past year.  The patient has a history of hypertension, but medical history is otherwise unremarkable.  He is a lifetime nonsmoker.  His father died of a "heart attack" at age 70.  Blood pressure is 144/74 mm Hg, and pulse is 72/min and regular.  Cardiac auscultation reveals a 3/6 ejection-type, late-peaking systolic murmur and a barely audible S2.  The murmur diminishes in intensity during the straining phase of the Valsalva maneuver.  Which of the following processes underlies this patient's current condition?

Quizplus · Accepted Answer

11ec160b_38bb_b605_9249_93f8792b141f_MD0001_00 This patient's soft S2 and late-peaking systolic ejection murmur that decreases in intensity with maneuvers that decrease left ventricular blood volume (eg, abrupt standing, Valsalva straining phase) are consistent with aortic stenosis, which most commonly occurs due to age-related calcific aortic valve disease (CAVD). The early pathogenesis of CAVD is analogous to that of arterial atherosclerosis.xa0 The endothelium lining the aortic side of the aortic valve cusps is exposed to the same high pressure and turbulent blood flow as the aortic vascular endothelium.xa0 As occurs with atheroma development in the vascular endothelium, these mechanical forces (along with smoking, hyperglycemia, and hyperlipidemia) over time cause damage to the aortic valve cusp endothelium, triggering endothelial dysfunction and the onset of a similar atherosclerotic process.xa0 There is subendothelial lipid deposition and infiltration of inflammatory cells (ie, macrophages, T lymphocytes) followed by the release of inflammatory mediators (eg, interleukin-1-beta, transforming growth factor beta-1). Subsequently, there is increased production of proteins involved in tissue calcification (eg, osteopontin).xa0 Fibroblasts differentiate into osteoblast-like cells, leading to aberrant bone matrix deposition with progressive valvular calcification and stenosis. (Choice A)xa0 Cardiomyocyte hypertrophy and disarray with asymmetric septal thickening occurs in hypertrophic cardiomyopathy.xa0 As with aortic stenosis, patients have a harsh crescendo-decrescendo systolic murmur; however, the murmur increases (rather than decreases) in intensity with maneuvers that reduce left ventricular blood volume. (Choice C)xa0 Myxomatous valve thickening and elastin fragmentation is typically seen in mitral valve prolapse.xa0 Patients have a nonejection systolic click and a mid-to-late systolic murmur that occurs earlier in systole with decreases in left ventricular blood volume. (Choice D)xa0 Subendocardial granulomatous lesions with fibrinoid necrosis and subsequent fibrosis are seen in patients with rheumatic heart disease.xa0 Patients with rheumatic aortic stenosis typically have mitral valve involvement as well, which would be evidenced by a murmur of mitral stenosis or regurgitation. (Choice E)xa0 Inflammation of valvular endothelium with deposition of sterile platelet thrombi is seen in nonbacterial thrombotic endocarditis (also known as marantic, verrucous, or Libman-Sacks endocarditis).xa0 The mitral or aortic valve is typically involved, usually leading to regurgitation rather than stenosis. Educational objective: Aortic stenosis most commonly results from age-related calcific aortic valve disease (CAVD).xa0 The early pathogenesis of CAVD closely mimics that of arterial atherosclerosis.xa0 In the later stages, fibroblasts differentiate into osteoblast-like cells and deposit bone matrix, leading to progressive valvular calcification and stenosis. __________ References: Human aortic valve calcification is associated with an osteoblast phenotype. (http://www.ncbi.nlm.nih.gov/pubmed/12719282) Bone formation and inflammation in cardiac valves. (http://www.ncbi.nlm.nih.gov/pubmed/11257079) Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. (http://www.ncbi.nlm.nih.gov/pubmed/15967862)

A 68-Year-Old Man Comes to the Office Due to Exertional