The Pathogenesis and Treatment of the Valvulopathy of Aortic Stenosis: Beyond the SEAS

Elmariah, Sammy; Mohler, Emile R.

doi:10.1007/s11886-010-0089-6

Cited by 22 publications

(14 citation statements)

References 49 publications

(66 reference statements)

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“…An analogous situation is the use of statin therapy for calcific aortic stenosis. This appeared promising in several retrospective studies but did not show efficacy in a large randomized prospective study(23) leading many to conclude that therapy with statins failed because it was given too late in the progression of the disease. Thus, future studies of treatments for alkaptonuria will also need to consider that therapy for the cardiovascular complications of alkaptonuria may be more effective at an early stage.…”

Section: Discussionmentioning

confidence: 99%

Aortic stenosis and vascular calcifications in alkaptonuria

Hannoush

Introne

Chen

et al. 2012

Molecular Genetics and Metabolism

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Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports . We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications.

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Section: Discussionmentioning

confidence: 99%

Aortic stenosis and vascular calcifications in alkaptonuria

Hannoush

Introne

Chen

et al. 2012

Molecular Genetics and Metabolism

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“…Calcification of the aortic and mitral valves is a progressive disease similar to atherosclerosis(1-4) that is associated with adverse cardiovascular outcomes. (5-7) Even without hemodynamically significant valve obstruction, calcific aortic and mitral valve disease have been associated with dramatic increases in the risk of myocardial infarction, stroke, and cardiovascular and all-cause mortality.…”

Section: Introductionmentioning

confidence: 99%

Associations of LV Hypertrophy With Prevalent and Incident Valve Calcification

Elmariah

Delaney

Bluemke

et al. 2012

JACC: Cardiovascular Imaging

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Objectives We aim to evaluate the relationship between percent of predicted left ventricular mass (%PredLVM) and valve calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Background Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood. Methods MESA is a longitudinal cohort study of men and women aged 45-84 years without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling. Results Prevalent AVC was observed in 630 and MAC in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, gender, body mass index, ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (OR=1.18 per SD increase in %PredLVM [95%CI 1.08 – 1.30]; p=0.0004) and MAC (OR=1.18 [95%CI 1.06 – 1.32]; p=0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95%CI 0.15 – 0.38]; p<0.0001) and MAC (risk difference = 0.20 [95%CI 0.03 – 0.37]; p=0.02). During follow-up (mean 2.4±0.9 years), 153 subjects (4%) developed AVC and 198 (5%) MAC. %PredLVM was associated with incident AVC (OR=1.24 [95%CI 1.04 – 1.47]; p=0.02) and MAC (OR=1.18 [1.01-1.40]; p=0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification. Conclusions Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders.

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“…Calcific AS is characterized by an active, progressive process similar to atherosclerosis that involves basement membrane disruption, inflammatory cell infiltration, lipid deposition, and calcification [2,8]. As the valve leaflets thicken, their mobility decreases, resulting in a narrowed valve orifice.…”

Section: Compensatory LV Response To Asmentioning

confidence: 99%

“…Calcific aortic valve disease, which often progresses to severe aortic stenosis (AS), is the most common cause of valvular heart disease in the Western world, present in over 20 % of older adults [1,2]. With worsening AS, symptoms including angina, syncope, and heart failure develop.…”

Section: Introductionmentioning

confidence: 99%

Patterns of Left Ventricular Remodeling in Aortic Stenosis: Therapeutic Implications

Elmariah

2015

Curr Treat Options Cardio Med

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Aortic valve stenosis is characterized by indolent progression followed by the late development of symptoms once left ventricular compensatory mechanisms fail. In this review, we describe the left ventricular response to aortic stenosis. Specifically, we highlight the process of adaptive remodeling, which begins as a beneficial compensatory mechanism but ultimately transitions to a maladaptive process characterized by inappropriate left ventricular hypertrophy, interstitial fibrosis, and diminished contractility. Myocardial fibrosis ensues as the remodeling process progresses with potentially irreversible consequences on diastolic and systolic function and on clinical symptoms and outcomes. Recent data suggest that fibrosis is largely responsible for the development of symptoms in patients with severe aortic stenosis, which unfortunately implies that fibrosis may be advanced by the time clinical symptomatology triggers evaluation for aortic valve replacement. Interstitial fibrosis persists for years after valve replacement and, when severe, can lessen the clinical benefits of valve replacement. Further evaluation of noninvasive measures capable of assessing the extent of maladaptive left ventricular remodeling and of predicting its reversal are desperately needed in order to enhance the personalized delivery of aortic valve replacement for severe aortic stenosis. We support aggressive assessment of symptomatic status with more frequent clinical follow-up and exercise testing in asymptomatic individuals with severe left ventricular hypertrophy or impaired longitudinal contractility. However, whether early valve replacement is advantageous in patients with evidence of maladaptive left ventricular remodeling in the absence of symptoms remains unknown, but is certainly worthy of further investigation.

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The Pathogenesis and Treatment of the Valvulopathy of Aortic Stenosis: Beyond the SEAS

Cited by 22 publications

References 49 publications

Aortic stenosis and vascular calcifications in alkaptonuria

Aortic stenosis and vascular calcifications in alkaptonuria

Associations of LV Hypertrophy With Prevalent and Incident Valve Calcification

Patterns of Left Ventricular Remodeling in Aortic Stenosis: Therapeutic Implications

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