Rosuvastatin slows the development of diastolic dysfunction in calcific aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aims were to test the effect of rosuvastatin on the progression of left ventricular (LV) diastolic function in patients with aortic stenosis (AS), and to evaluate the use of beta-natriuretic-peptide (BNP) as a marker of diastolic dysfunction in this condition. METHODS: Sixty-one hypercholesterolemic, consecutive new referrals with moderate AS were administered rosuvastatin (Crestor) 20 mg/day for 18 months, while a further 60 subjects with normal cholesterol levels remained untreated. The LV diastolic function was determined using conventional Doppler echocardiography, tissue Doppler imaging (TDI); BNP plasma levels were monitored when subjects entered the study and then assessed prospectively at six-month intervals until the study end. RESULTS: After an 18-month (mean 73 +/- 24 weeks) period of treatment with rosuvastatin (Tx group), patients showed a significantly better diastolic function than untreated subjects (uTx group), as indicated by an isovolumic relaxation time (IVRT) (Tx 102.0 +/- 42.8 versus 97.2 +/- 19.1; p < 0.001; uTx 99.7 +/- 21.7 versus 95.2 +/- 21.8 ms; p = 0.032), E/A ratio (Tx 1.0 +/- 0.6 versus 0.9 +/- 0.3, p = 0.52; uTx 1.2 +/- 0.40 versus 0.9 +/- 0.30 versus, p = 0.006), and E/E' ratio (Tx 11.4 +/- 1.5 versus 11.4 +/- 1.8, p = 0.19; uTx 15.4 +/- 1.2 versus 12.3 +/- 1.5, p < 0.001). Similarly, at study end, plasma levels of BNP were significantly lower in the Tx group than in the uTx group [median (1st-3rd quartiles): 37.0 pg/ml (20.1-65.2 pg/ml) versus 57.1 pg/ml (46.9-98.2 pg/ml); p = 0.017]. CONCLUSION: The results of this prospective follow up study of asymptomatic patients showed that rosuvastatin treatment delays the progression of diastolic dysfunction in moderate AS when assessed using hemodynamic echocardiographic parameters or by the release of plasma physiological markers. Hence, the benefits of statin treatment in AS, which are known to affect the valve endothelium, also extend to changes affecting myocardial function itself.

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.

Natriuretic peptides in aortic stenosis.

Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries. Diagnosis, risk stratification and monitoring are usually based on clinical and echocardiographic parameters. Complementary methods are needed to improve management and outcome, particularly in patients with severe asymptomatic AS, whose management remains controversial. Natriuretic peptides (NPs) have established value as biomarkers in heart failure, coronary heart disease and pulmonary hypertension. This review discusses the usefulness and prognostic value of natriuretic peptides in AS. B-type natriuretic peptide (BNP) and its prohormone (NT-proBNP) correlate with disease severity, development of symptoms and prognosis, but before they can be routinely used in clinical practice, additional prospective studies are needed.

Effect of hydroxymethylglutaryl coenzyme-a reductase inhibitors on the long-term progression of rheumatic mitral valve disease.

BACKGROUND: At present, no medical therapy is known to affect the progression of rheumatic mitral stenosis (MS). We sought to assess the effect of statin treatment on long-term progression of MS in a large population. METHODS AND RESULTS: From our 20-year database, we identified all patients with rheumatic MS with > or =2 echocardiographies > or =1 year apart. Exclusion criteria were previous intervention on the mitral valve, more than moderate aortic regurgitation, or symptoms at first examination. The study sample included 315 patients (mean age, 61+/-12 years; 224 women); 35 patients (11.1%) were treated with statins, and 280 (88.9%) were not. Mean follow-up period was 6.1+/-4.0 years (range, 1 to 20). The rate of decrease in mitral valve area was significantly lower in the statin group compared with the untreated group (0.027+/-0.056 versus 0.067+/-0.082 cm(2)/y; P=0.005). The annualized change in mean transmitral gradient was lower in statin-treated patients (0.20+/-0.59 versus 0.58+/-0.96 mm Hg/y; P=0.023). The prevalence of fast MS progression (annual change in mitral valve area >0.08 cm(2)) was significantly lower in the statin group (P=0.008). An increase in systolic pulmonary artery pressure of >10 mm Hg was found in 17% of patients in the statin group versus 40% of untreated patients (P=0.045). CONCLUSIONS: Our study shows a significantly slower progression of rheumatic MS in patients treated with statins. These findings could have an important impact in the early medical therapy of patients with rheumatic heart disease.

Analysis of variability and reproducibility of echocardiography measurements in valvular aortic valve stenosis.

BACKGROUND: Doppler echocardiography is the most frequent method for detecting and evaluating the severity of valvular aortic stenosis. The aim of this study was to assess the variability and reproducibility of echocardiographic parameters including aortic valve area (AVA), peak aortic jet velocity (V(max)), velocity ratio (V(LVOT)/V(max)), peak gradient (G(max)) and mean gradient (G(mean)) in aortic stenosis (AS) patients. METHODS: Doppler echocardiograms were obtained from 150 randomly selected patients (56.7% male; mean age 73 +/- 9 years) with asymptomatic moderate aortic valve stenosis. The echocardiographic measurements were performed by two independent level III (expert) blinded observers. To assess intra-observer variability, we evaluated parameters of AS progression at two different times (mean of two weeks after the first examination). RESULTS: For intra-observer variability (observer 1), the variation and reproducibility coefficients were, respectively, 1.88% and 0.16 m/s for V(max), 2.08% and 0.14 for V(LVOT)/V(max) 2.05% and 0.18 cm2 for AVA, 3.89% and 5.18 mmHg for G(max) and 7.87% and 6.30 mmHg for G(mean). For inter-observer variability, the variation and reproducibility coefficients were, respectively, 2.00% and 0.14 m/s for V(max), 2.91% and 0.14 for V(LVOT)/V(max), 7.67% and 0.16 cm2 for AVA, 8.53% and 7.06 mmHg for G(mean) and 3.90% and 5.58 mmHg for G(max). Both intra- and inter-observer studies showed excellent intraclass correlation coefficients (ICC) for all echocardiographic parameters (ICC ranged from 0.943 to 0.990 for intra-observer variability and from 0.955 to 0.992 for interobserver variability). CONCLUSION: Doppler echocardiographic measurements of AVA, V(max), G(max) and G(mean) are highly reproducible when performed by expert observers. Of all echocardiographic parameters, V(max) and V(LVOT)/V(max) showed the best variability and reproducibility, and thus constitute reliable tools for clinical and research purposes in aortic stenosis diagnosis and follow-up.

[Bicuspid aortic valve and aortic disease: past, present and future]. / Válvula aórtica bicúspide e aortopatia: o passado, o presente e o futuro [121].

Bicuspid Aortic Valve is the most common cardiac congenital abnormality occurring in 1% to 2% of the general population. The acquired bicuspid valve has been considered by some authors to be a rheumatic disease consequence. Meanwhile, some recent experimental studies where atrioventricular valves have been studied for the presence of rheumatic stigmata have excluded this hypothesis. There are some theories that can explain the genesis of this disease but actually Bicuspid Aortic Valve is often considered a benign lesion early in life, but its valvular and vascular complications result in considerable morbidity and mortality later in life. Beside beta-blockers, there are some drugs that are being study and may be used in a nearly future for slower disease progression, although the definitive treatment still is the cardiac valve replacement surgery.

Bench to bedside defining calcific aortic valve disease: osteocardiology.

INTRODUCTION: For years, calcific aortic valve disease (CAVD) was thought to be due to a degenerative process, but recent scientific discoveries have proven it to be an active process. Understanding the cellular mechanisms for the development of disease and translating the cellular changes critical in the development of calcific phenotypes. The use of multimodality imaging has been the gold standard to define the development of calcification to determine the timing of therapy. AREAS COVERED: This review will discuss the scientific literature in a new and evolving field known as osteocardiology, which specifically defines the cellular mechanisms involved in the development of the osteogenic phenotype in the heart and vasculature. The work in this field has been highlighted by the calcific aortic valve disease working group at the NIH. This review will discuss the appropriate use criteria for multimodality imaging techniques to identify early cellular and hemodynamic disease progression in the aortic valve to help determine the timing of therapy, the osteocardiology theory. EXPERT OPINION: The authors will provide their background in basic science and clinical medicine to support the opinions in this paper.

The role of statins in aortic stenosis. Myth or reality?

Our understanding of aortic valve disease has improved in the past decade from considering it a degenerative process to the realization that it is an active biologic disease. Aortic valve disease, although it has a similar atherosclerotic pathogenesis to vascular disease, differs in terms of bone calcification. Determining the appropriate timing of statin therapy to slow the progression of bone formation in these lesions is essential for the routine use of these drugs in such patients. Knowledge of the biology of valve lesions will play an important part in understanding this disease and future treatment options for these patients.

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 R(2) = 0.27). The percent change in the AVA for the treated patients was 5% and 15% for the nontreated patients (p = 0.579 and R(2) = 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).

Valvular heart disease and 3-dimensional echocardiography: ready for prime-time?

Significant advances in 3-dimensional echocardiography (3DE) technology have ushered its use into clinical practice. The recent advent of real-time 3DE using matrix array transthoracic and transesophageal transducers has resulted in improved image spatial resolution, and therefore, enhanced visualization of the patho-morphological features of the cardiac valves. Three-dimensional echocardiography provides unique perspectives of valvular structures by presenting "en face" views of valvular structures, allowing for a better understanding of the topographical aspects of pathology, and a refined definition of the spatial relationships of intracardiac structures. Three-dimensional echocardiography makes available indices not described by 2D echocardiography and has been demonstrated to be superior to 2D echocardiography in a variety of valvular disease scenarios. In this review, we discuss the incremental role of 3DE in evaluating valvular anatomic features, volumetric quantification, pre-surgical planning, intra-procedural guidance, and post-procedural assessment of valvular heart disease.

Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis.

INTRODUCTION AND OBJECTIVES: Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression. METHODS: We investigated the association between PON1 55 and 192 single nucleotide polymorphisms (SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67 consecutive patients with moderate CAVS and 251 healthy controls. RESULTS: PON1 paraoxonase activity was higher in CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein (P=0.24) or low-density lipoprotein cholesterol (P=0.52). CONCLUSION: The PON1 genotype Q192R SNP has an important effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique population.

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.