Coronary Artery Disease: Otto CM

Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS, Nishimura RA, Carabello BA, Faxon DP, Freed MD, Lytle BW, O'Gara PT, O'Rourke RA, Shah PM, Anonymous00383. · No affiliation provided · J Am Coll Cardiol. · Pubmed #18848134 No free full text.

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Anonymous00282, Anonymous00283, Anonymous00284, Anonymous00285, Bonow RO, Carabello BA, Kanu C, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B. · No affiliation provided · Circulation. · Pubmed #16880336 links to  free full text

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Otto CM. · Division of Cardiology, University of Washington, Seattle, Washington 98195-6422, USA. · J Am Coll Cardiol. · Pubmed #14736433 No free full text.

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Otto CM, O'Brien KD. · No affiliation provided · Heart. · Pubmed #11359728 links to  free full text

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Otto CM. · Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington 98195, USA. · J Am Coll Cardiol. · Pubmed #16750677 No free full text.

Abstract: Standard echocardiographic evaluation of aortic stenosis (AS) severity includes measurement of aortic velocity, mean transaortic pressure gradient, and continuity equation valve area. Although these measures are adequate for decision making in most patients, there is no single value that defines severe stenosis. Aortic stenosis affects not just the valve, but the entire vascular system, including the left ventricle (LV) and systemic vasculature. More sophisticated measures of disease severity might explain the apparent overlap in hemodynamic severity between symptomatic and asymptomatic patients and might better predict the optimal timing of valve replacement. There have been several approaches to evaluation of stenosis severity based on valve hemodynamics, the ventricular response to increased afterload, ventricular-vascular coupling, or the systemic functional consequences of valve obstruction, such as exercise testing and serum brain natriuretic peptide levels. Aortic valve replacement is indicated when symptoms due to severe AS are present. In most asymptomatic patients, the risk of surgery is greater than the risk of watchful waiting so that management includes patient education, periodic echocardiography, and cardiac risk factor modification. Many adults with AS have comorbid conditions that affect both the diagnosis and management of the valve disease, including aortic regurgitation, aortic root dilation, hypertension, coronary artery disease, LV dysfunction, and atrial fibrillation. Comorbid conditions should be evaluated and treated based on established guidelines, although awareness of the potential effects of therapy in the presence of valve obstruction is needed.

Branch KR, O'Brien KD, Otto CM. · Division of Cardiology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356422, Seattle, WA 98195-6422, USA. · Curr Cardiol Rep. · Pubmed #11827633 No free full text.

Abstract: Aortic sclerosis is a calcific disease of the aortic valvular leaflets defined as focal leaflet thickening without significant obstruction to left ventricular outflow. Several clinical factors are associated with calcific aortic valve disease, including male sex, smoking, hypertension, age, hypercholesterolemia, and diabetes. Histologic and biochemical studies suggest similarities between the mechanisms involved in the development of aortic sclerosis and atherosclerosis, suggesting these two diseases may share common pathophysiologic mechanisms. In a recent prospective trial, the presence of aortic sclerosis was associated with an approximately 50% increase in cardiovascular mortality and myocardial infarction, even after correction for age, gender, known coronary artery disease, and clinical factors associated with a aortic sclerosis.

Aikawa K, Otto CM. · Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA. · Prog Cardiovasc Dis. · Pubmed #11431802 No free full text.

Abstract: In adults with valvular stenosis, the importance of prompt aortic valve replacement once symptoms occur is well known. The operative mortality for aortic valve replacement has improved dramatically over the past 4 decades and remains the only effective therapy for severe symptomatic aortic stenosis. Aortic valve replacement in patients with left ventricular dysfunction has a high operative mortality, although those patients who do not undergo surgery at all have an even worse outcome. While issues to consider include the presence or absence of coronary artery disease and expected hemodynamics of the prosthetic valve compared with the native valve, when in doubt, one should err on the side of surgical intervention. Elderly age is not a contraindication to aortic valve replacement for severe symptomatic aortic stenosis, although there is a higher prevalence of comorbid disease and higher operative mortality. Life expectancy is significantly prolonged and quality of life is significantly improved in the elderly who survive surgery. Indications for surgery in asymptomatic patients are controversial. We do not recommend valve replacement in asymptomatic patients at this time due to the known risks of surgery and a prosthetic valve and the lack of evidence for benefit of early surgery. Patients undergoing coronary bypass surgery should be considered for concomitant aortic valve surgery for moderate aortic stenosis that is expected to progress to severe stenosis in less than 5 years.

O'Brien KD, Zhao XQ, Shavelle DM, Caulfield MT, Letterer RA, Kapadia SR, Probstfield JL, Otto CM. · Division of Cardiology, University of Washington, Seattle, WA 98195-6422, USA. · J Investig Med. · Pubmed #15222408 No free full text.

Abstract: BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor use is presumed to be contraindicated in patients with aortic stenosis (AS). We determined the hemodynamic effects of ACE inhibitors in patients with mild to moderate aortic stenosis (AS) and preserved left ventricular function. METHODS: Thirteen elderly patients (mean [SD] age = 65 [17] years), with mild to moderate AS (aortic jet velocity 2.5-4.0 m/s), normal left ventricular and renal function, and no clinical coronary artery disease, were enrolled in a single-center, open-label trial comparing the hemodynamic effects at baseline and following titration of ramipril to a maximum dose of 7.5 mg twice daily. Patients were identified from echocardiography laboratory logs. Despite a presumed contraindication to ACE inhibitor use in AS patients, 30% (71 of 235) of patients otherwise meeting inclusion or exclusion criteria were excluded owing to current ACE inhibitor use. Patients were monitored with weekly clinic visits, biweekly laboratory tests, and monthly echocardiograms. RESULTS: There were no significant changes from baseline to week 8 in echocardiographic parameters, including mean (SD) aortic jet velocity [2.9 (0.4) vs 2.9 (0.4) m/s], calculated aortic transvalvular gradient [18 (6) vs 18 (6) mm Hg], or cardiac output [5.5 (1.2) vs 6.0 (2.1) L/min], or significant changes in blood pressure or heart rate. Early discontinuations were for asymptomatic low blood pressure (one patient) or a reversible creatinine increase of 0.3 mg/dL (one patient). CONCLUSIONS: Short-term treatment with up to 7.5 mg twice daily of ramipril was well tolerated in patients with mild to moderate AS and preserved left ventricular function. A surprisingly high proportion of patients with documented AS were already receiving ACE inhibitors.

O'Brien KD, Shavelle DM, Caulfield MT, McDonald TO, Olin-Lewis K, Otto CM, Probstfield JL. · Division of Cardiology, University of Washington, Seattle 98195-6422, USA. · Circulation. · Pubmed #12390952 links to  free full text

Abstract: BACKGROUND: Recent studies have demonstrated that lesions of aortic sclerosis and stenosis share several similarities with lesions of atherosclerosis. In atherosclerosis, angiotensin-converting enzyme (ACE) is expressed by a subset of macrophages. This study was undertaken to determine whether ACE might be present in aortic sclerosis or stenosis lesions. METHODS AND RESULTS: Immunohistochemistry was performed on 26 paraffin-embedded human aortic valves. Monospecific antibodies were used to identify ACE, macrophages, angiotensin II type 1 receptor (AT-1 receptor), angiotensin II, and apolipoprotein B. Human low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were isolated from plasma of normal volunteers by sequential density-gradient ultracentrifugation. ACE was not present in normal valves but was present in all valves with aortic sclerosis or stenosis lesions. ACE was detected on a subset of lesion macrophages but was present primarily in an extracellular distribution, where it colocalized with apolipoprotein B. ACE was detected by Western blotting on plasma LDL but not on HDL isolated from normal volunteers. Angiotensin II, the enzymatic product of ACE, was colocalized with ACE in valve lesions. ACE also was colocalized with apolipoprotein B in an adjacent coronary atherosclerotic plaque. CONCLUSIONS: ACE is present in aortic sclerosis and stenosis lesions, where it may participate in lesion development, as is evidenced by the presence of its enzymatic product, angiotensin II. The observation of an association of ACE with LDL in both lesions and plasma suggests that LDL may deliver ACE to lesions and has implications for the role of ACE-containing LDL in other diseases, such as atherosclerosis.