Luis M Moura

New cardiovascular biomarkers: clinical implications in patients with valvular heart disease

Valvular heart disease (VHD) is characterized by an ongoing, inflammatory cellular response which results in a left ventricular hemodynamic stress change in response to valvulopathy. The current inflammatory hypothesis suggests that as the heart valve disease progresses the inflammatory cytokine response is activated causing continuation of deleterious effects on the heart and vasculature. This can lead to progression of heart failure and left ventricular dysfunction. Over the last 10 years, a number of biologically active molecules, termed biomarkers, have been discovered in VHD. These can be used to detect the progression and pathogenesis of heart failure and to assess the severity of inflammation (e.g., C-reactive protein). Brain natriuretic peptide (BNP) can diagnose underlying cardiac systolic and diastolic dysfunction. In high-risk patients BNP is also considered to be a useful tool for assisting in the diagnosis and monitoring the progression of VHD. Patients with symptomatic VHD benefit from aortic valve surgery; however, management in the absence of symptoms remains challenging. While the lack of symptoms can delay aortic valve replacement, unselected premature aortic valve replacement may be associated with unbalanced risks of cardiac surgery. This review summarizes the current and emerging clinical and potential research application of specific biomarkers of VHD.

New understanding about calcific aortic stenosis and opportunities for pharmacologic intervention.

Purpose of review This review article will discuss aortic stenosis, the evolving studies defining the cellular mechanisms and the potential for medical therapies for the treatment of this disease. Recent findings Currently, the only therapy for these patients is surgical valve replacement. In the past decade there has been a change in the paradigm towards our understanding of the cellular biology of this disease process. Studies in laboratories across the world have demonstrated that this disease has an active biology and that this biology may be targeted with medical therapies similar to that of vascular atherosclerosis. Summary Calcific aortic stenosis is the third most common form of cardiovascular disease in the USA. It has replaced rheumatic heart disease in prevalence in western countries due to improved access to healthcare and the widespread use of antibiotics.

Valvular lesions in patients with systemic lupus erythematosus and antiphospholipid syndrome: An old disease but a persistent challenge

Valvular heart disease is common in systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Immunologic insult plays a fundamental role in its pathogenesis but data on the role of antiphospholipid antibodies have been inconsistent, particularly regarding SLE-associated valvular lesions. Although timely diagnosis is essential to prevent progression of valvular lesions, treatment remains a challenge because of the lack of large systematic studies. This article reviews and summarizes recent information relating to valvular damage in these two autoimmune diseases, and highlights some important questions that need to be answered.

The Lipid Hypothesis in Calcific Aortic Valve Disease The Role of the Multi-Ethnic Study of Atherosclerosis

Calcific aortic valve disease (CAVD) is the most common indication for valve intervention in the world.1 The cellular mechanisms, cardiovascular risk factors, and therapeutic interventions have been under intense investigation in the 21st century. In the study published in ATVB , Cao et al2 tested the Multi-Ethnic Study of Atherosclerosis (MESA) database to define the calcification phenotype associated with unique lipoprotein mechanisms in the development of calcification. MESA was designed to test subclinical atherosclerosis markers and measure calcification burden in the aortic valve using computed tomography measurements. The study group included individuals from age 45 to 84 years, who were free of any clinical cardiovascular disease and treated diabetes mellitus.3,4 The database is robust to test for subclinical risk factors in the development of calcific aortic valve disease. See accompanying article on page 1003 O’Brien et al5 and Otto et al6 publish studies to define the role of lipoproteins in ex vivo calcified aortic valves. Over the next 20 years, studies in the field of calcific aortic valve disease have determined that the calcific aortic valve disease is not a degenerative process, but an active cellular biology. …

SALTIRE-RAAVE: targeting calcific aortic valve disease LDL-density-radius theory

SALTIRE and RAAVE were the first two studies to evaluate the use of statin therapy for impeding calcific aortic valve disease (CAVD). This review presents the findings of low-density lipoprotein (LDL)-density-radius theory as tested using the combined results from the SALTIRE and RAAVE studies. Patients who received statin therapy had a greater degree of LDL cholesterol lowering, seen as the % change in LDL (47 vs 2%, p = 0.012), which in itself was significantly associated with a lesser change in aortic valve area (AVA; p < 0.001 and R2 = 0.27). The percent change in the AVA for the treated patients was 5% and 15% for the nontreated patients (p = 0.579 and R2 = 0.03). In summary, these published findings suggest that when applying the LDL-density-radius theory, which combines the cellular biology and the hemodynamics as defined by the continuity equation for AVA, there may be a role for lipid-lowering therapy in contemporary patients with calcific aortic valve disease (CAVD).

Role of Statins in Valvular Heart Disease: Rheumatic Valve Disease and Bioprosthetic Valves

Although rare nowadays in North America and Europe, rheumatic heart disease (RHD) continues to be an important healthcare problem in developing countries with an estimated prevalence of 15.6 million people worldwide and 470,000 newly diagnosed cases every year (Carapetis et al. 2005). Acute rheumatic fever leads to an abnormal immune response to the infection with rheumatogenic group A hemolytic streptococci leading to pancarditis with acute inflammation of the leaflets. Inflammation, fibrosis and calcification lead to alterations of the cusps and valvular apparatus, leading to mitral, aortic and/or tricuspid stenosis and/or regurgitation that will eventually become symptomatic. The mitral valve is commonly involved more often leading to mitral stenosis meanwhile isolated aortic or tricuspid involvement is rare (Marijon et al. 2007). Typical aspects of rheumatic involvement in valve disease are represented by adhesions and fusions of the commissures with cusp retraction and stiffening of the free borders of the cusps (Bonow et al. 2006).

Coronary Flow Reserve and Myocardial Contrast Echocardiography

Although there are several diagnostic techniques available for assessing coronary function, the quantification of coronary flow (CF) and coronary flow reserve (CFR) by angiography using an intracoronary Doppler flow wire is usually invasive. Recently, there have been several advances in echocardiography, not only in the direct visualization of the coronary arteries, but also in measuring CF and CFR. In this chapter, the current state of myocardial contrast echocardiography will be revisited, as well as the measurement of CF and CFR by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE), with special emphasis on recent advancements in ultrasound contrast-enhanced agents.