Prevalence Of Aortic Valve Disease Research Articles

Nitisinone attenuates progression of aortic stenosis in patients with alkaptonuria: an analysis of the SONIA 2 study

Abstract Background/introduction Alkaptonuria (AKU) is a rare metabolic disorder caused by a defective enzyme, resulting in deposition of unmetabolised homogentisic acid in various connective tissues throughout the body (also termed "ochronosis"). Ochronosis of the aortic valve leading to progressive aortic stenosis is a rare but serious complication. Nitisinone decreases urinary and serum homogentisic acid levels and has been shown to improve morbidity and slow disease progression in AKU but the effects of this treatment on the progression of aortic stenosis have not yet been described. This review extrapolated from the data set of the SONIA 2 study, a 4-year multi-centre, randomised controlled trial investigating the effect of nitisinone on a composite clinical measure of AKU disease activity, but looked more specifically at measures of aortic stenosis disease progression. Methods Data was obtained from echocardiograms performed on 138 patients at baseline, 12, 24, 36 and 48 months of follow-up. In measuring the degree of aortic stenosis, the peak trans-aortic velocity (Vmax) was examined. A linear mixed effects regression model was used to assess the association between treatment and Vmax and to ascertain the difference in this measure at baseline and 48 months between the treatment and control groups. The mixed effects model incorporated both fixed effects for population parameters (age, sex, baseline Vmax, follow-up time) and treatment; and random effects, to account for intra-subject correlation of longitudinal observations of Vmax, inter-subject variability of baseline measurements of Vmax, and centre. Results At baseline, 19/138 patients (13.8%) had aortic stenosis, as classified by echocardiogram findings in accordance with the European Society of Cardiology (ESC) guidance on valvular heart disease, with 9/19 having mild aortic stenosis, 6/19 having moderate aortic stenosis and 4/19 having severe aortic stenosis. 25/138 had aortic sclerosis (see figure 1). The prevalence of aortic valve disease increased with age. From the 4-year follow-up period, 613 longitudinal observations of 138 subjects across all sites were obtained. At baseline, the difference in Vmax between the control and treatment groups was 0.063 m/s [95% CI: -0.054 m/s to 0.18 m/s] and did not reach statistical significance (p=0.23). At the end of the 4-year treatment period, the difference in Vmax was 0.10 m/s [95% CI: -0.0007 m/s to 0.20 m/s] and was statistically significant (p=0.05) (see figure 2). Conclusion Nitisinone slowed progression of aortic stenosis in patients with AKU. This may be grounds for timely initiation of nitisinone in those deemed to be at high risk, as identified by echocardiography. Of note, this is the first time that any medical therapy has ever been shown to affect the natural history of aortic stenosis.

All Aortic Valve Diseases Taken Together Are Not Associated With Obesity.

Obesity is a risk factor for cardiovascular disease. The goal of this study was to evaluate any association between aortic valve disease and obesity using a very large database. The Nationwide Inpatient Sample database was utilized for statistical analysis using ICD-9 codes for aortic valve disease and obesity in the United States from 2003 to 2007. A 25% random sample of nonobese patients was used for comparison of aortic valve disease prevalence during the same 5-year period. A total of 1,971,812 patients with obesity were identified from 2003 to 2007. Comparing this population with a random sample of nonobese patients during the same years, there was no significant difference between obese and nonobese patients in regards to the prevalence of aortic valve disease (1.1-1.2% in 2003 and 2004, 1.2% in 2005-2007, P = NS). After adjusting for age, gender, and race, obesity was associated with lower prevalence of aortic valve disease in 2003-2007 (odds ratio 0.81-0.86, P < 0.01). Using a very large database, we found a decrease in the prevalence of aortic valve disease in the obese population. This suggests that obesity alone does not pathologically affect the aortic valve.

Aortic valve neocuspidization using autologous versus bovine pericardium: Ozaki versus Batista.

The average living age of the population is constantly increasing and so is the incidence and prevalence of aortic valve disease. Surgical aortic valve replacement (SAVR) is the current gold standard treatment. Nevertheless, the use of prosthetic valves in SAVR is associated with issues that impact patients' quality of life. Aortic valve neocuspidization (AV Neo) offers a means to solve this dilemma by minimizing foreign valve tissue. AV Neo can either be performed using glutaraldehyde-treated autologous pericardium (Ozaki procedure) or bovine pericardium (Batista procedure). This commentary aims to discuss the recent study by Chan and colleagues which highlighted the surgical approach, clinical outcomes, and limitations of the Ozaki procedure, and compare this to the Batista procedure. A comprehensive literature search was performed using multiple electronic databases including PubMed, Ovid, Embase, and Scopus to collate the relevant research evidence. Although the Ozaki procedure can achieve favorable results whilst mainly avoiding the need for life-long oral anticoagulation with mechanical valves, it still has several limitations that may hinder results. AV Neo using glutaraldehyde-treated bovine pericardium, developed by pioneer cardiac surgeon Dr. Randas J. Vilela Batista, yields superior clinical outcomes to Ozaki's, including excellent survival, lower complications, and minimal need for reoperation as well as shorter operative times. AV Neo offers a means to perform SAVR whilst escaping the prosthetic valve issues. However, the Batista procedure has shown beyond doubt that it can be considered the superior approach for AV Neo over the Ozaki procedure.

Idiopathic thrombocytopenic purpura is strongly associated with higher prevalence of aortic valve disease.

Aortic valve disease (AVD) has similarities to atherosclerosis in the case of aortic stenosis. The important role of platelet in the pathogenesis of atherosclerosis is known. The goal of this study is to evaluate whether platelet disorders play any role in aortic valve disease. We used patients with idiopathic thrombocytopenic purpura (ITP) for this study. We evaluated any association between ITP and AVD using a large inpatient database. The International Classification of Diseases, Ninth Revision, and Clinical Modification (ICD-9-CM) codes for ITP and AVD from the Nationwide Inpatient Sample (NIS) database were used for this study. Uni- and multivariate analyses were performed on data from 2002 to 2011 to evaluate any association between ITP and AVD. In the 2002 database, AVD was present in 1.73% of ITP patients versus 1.12% in the control population (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.34-1.81; p < 0.001). In the 2011 database, AVD was present in 1.96% of ITP patients versus 1.33% in the control population (OR, 1.48; 95% CI, 1.30-1.68; p < 0.001). ITP remained independently associated with AVD following a multivariate logistic regression analysis adjusting for age, gender, diabetes mellitus, hypertension, and hyperlipidemia in 2002 (OR, 1.35; 95% CI, 1.16-1.57; p < 0.001) with a trend of this association in 2011 (OR, 1.12; 95% CI, 0.98-1.27; p = 0.096). ITP was strongly associated with AVD over the 10-year period analyzed in a large inpatient database. The reason for this association is not known warranting further investigations.

Invited Commentary

Diseases of the aortic valve due to autoimmune disorders represent a challenge in more ways than one. Not only is the incidence of these conditions low, but the prevalence of aortic valve disease requiring intervention is even more rare. This makes it difficult to study and determine clinical patterns to inform surgical decision-making. In light of this, in this issue of The Annals of Thoracic Surgery, the study by Zhang and colleagues,1 from Fuwai Hospital in Beijing, is very informative and provides important insight.

Lifetime Risks of Valvular Heart Disease and Pacemaker Use in Patients With Ankylosing Spondylitis.

BackgroundThe likelihoods of valvular heart disease (VHD) and conduction abnormalities in patients with ankylosing spondylitis (ASp) are poorly defined. Knowing their lifetime risks of VHD and pacemaker use would help inform whether cardiac screening should be done.Methods and ResultsPatients with ASp and a comparison group without ASp were identified among US Medicare beneficiaries in 1999 to 2013. Frequencies of VHD and pacemaker use were compared in 4 age groups: 65 to 69 years, 70 to 74 years, 75 to 79 years, and 80 years or older, as were rates of valve surgeries, a measure of VHD severity, and new pacemaker insertions. Outcomes were compared between 42 327 patients with ASp and 19 211 703 patients without ASp. The prevalence of aortic valve disease in patients with ASp increased with age (2.6%, 6.7%, 10.9%, and 17.1%), as did the prevalence of mitral valve disease. Risks of VHD were slightly but significantly higher in patients with ASp (adjusted odds ratios 1.06–1.51). Rates of aortic valve replacement/repair were also higher in patients with ASp than in the comparison group (125 versus 93; 183 versus 149; 261 versus 208; 279 versus 191 per 100 000 patient‐years in the 4 age groups). Rates of mitral valve surgery did not differ between groups. Among patients with ASp, pacemaker use ranged from 1.0% to 7.6% across age groups, and was slightly higher than in controls (odds ratio range 1.11–1.32).ConclusionsLifetime risks of VHD and pacemaker use in ASp increase markedly with age, but are only slightly higher than in elderly people without ASp.

Newer echocardiographic techniques for aortic-valve imaging: Clinical aids today, clinical practice tomorrow.

Increasing life expectancy is expected to lead to a corresponding increase in the prevalence of aortic valve disease (AVD). Further, the number of indications for transcatheter aortic valve replacement (TAVR) as a treatment option for AVD is expanding, with a growing role for echocardiography in its management. In this review we summarize the current literature on some newer echocardiographic modalities and the parameters they generate, with a particular focus on their prognostic and clinical value beyond conventional methods in the management of aortic stenosis, TAVR, and aortic regurgitation. Speckle tracking and 3D echocardiography are now increasingly being used in the management of AVD. For instance, global longitudinal strain, the best-studied speckle tracking echocardiographic parameter, can detect subtle subclinical cardiac dysfunction in patients with AVD that is not apparent using traditional echocardiographic techniques. The emerging technique of 3D full volume color Doppler echocardiography provides more accurate measurement of the severity of aortic regurgitation than 2D-proximal isovelocity surface area. These novel techniques are promising for evaluating and risk stratifying patients to optimize surgical interventions, predict recovery, and improve clinical outcomes.

Frequency of Calcific Aortic Stenosis in Tertiary Care Hospital of Karachi

Background: Calcific aortic stenosis (AS) has become one of the most frequent types of Valvular Heart Disease (VHD) among elderly patients. Prevalence of aortic valve disease (AVD) increases with age and the incidence of calcific AS are on the rise as the general age of the population increases. Objectives: This study was conducted to find out the frequency of calcific AS in patients of tertiary care hospital. Methods: The cross sectional study was carried out in National Institute of Cardiovascular Disease (NICVD) during the period of January to December 2012 after institute approval. A total of 50 echocardiographically diagnosed elderly patients of calcific AS were included from OPD and echocardiography department. All patients were evaluated for clinical features, ECG, echocardiographic findings and outcome were noted and analyzed by using software SPSS version 21. Results: In our study we found 62% male and 38% female. The mean age was 67.12 years ± 5.08 with the range of 60 to 85 years. On echocardiography, out of 50 AS selected patients 18% had mild AS, 22% had moderate AS, and 60% had severe AS. One bicuspid aortic valve has been found. Conclusion: In elderly calcific AS constitutes a significant health problem. As the age advances it is an important cause of cardiovascular mortality and morbidity.

The leukotriene receptor antagonist montelukast and aortic stenosis

Aortic stenosis shares several characteristics with atherosclerotic lesions, such as inflammation and lipid accumulation leading to extensive calcification of the valvular leaflets, which eventually causes the aortic valve to narrow [1]. However, lipid lowering drugs of the statin class have not been shown to retard the progression of aortic stenosis. In fact, to date there is no medical treatment for this valvular heart disease and aortic stenosis remains the most common indication for surgical valve replacement [1]. Recently, the leukotriene pathway was shown to be associated with aortic stenosis. Local leukotriene production in calcified human valves increased reactive oxygen species production, activated osteogenic pathways and stimulated calcification [2]. In addition, the expression levels of leukotriene synthesizing enzymes within aortic valves were significantly correlated with the severity of aortic stenosis, as determined by echocardiography [2]. Leukotriene receptor antagonists (LTRA) are a well-established treatment of asthma. In addition, we recently showed that the therapeutic potential of anti-leukotriene drugs may go beyond asthma, based on the observation that the LTRA montelukast was associated with a decreased risk for recurrent cardiovascular events, such as stroke and myocardial infarction [3]. Taken together, these observations suggested that LTRAs may be protective for the development of aortic stenosis. To test this hypothesis, we have analyzed the incidence of aortic stenosis in relation to the use of montelukast. In brief, a nationwide population-based cohort of approximately 7 million Swedish residents integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational and Emigration Registers was followed from July 1 2005, to December 31 2008. The cohort and statistical methods have been described in detail in our previous studies [3, 4]. Analyses were performed in the whole adult population after exclusion of subjects with a prior diagnosis of aortic valve disease (ICD-10 code I35; ICD-9 code 4241; ICD-8 code 3659 and 4241). Montelukast exposure was defined from the national Swedish Prescribed Drug Register as claimed prescriptions of Anatomical Therapeutical Chemical (ATC) code R03DC03. Calculated from each dispense date, subjects were considered exposed for 3 months based on a prescription length of 3 months of use. Aortic stenosis (ICD-10 codes I35.0 and I35.2) was monitored as outcome and defined according to either the primary diagnosis or the primary cause of death, as recorded in the Patient and Cause of Death Registers. The associations between montelukast use and outcome were examined by Cox proportional hazard models estimating the hazard ratio (HR) of drug use, after adjustment for age, gender and socioeconomic factors (education level and income), the presence of respiratory disease and the use of drugs for respiratory and cardiovascular disease, as previously described [3] and detailed in supplementary Table S1. The prevalence of aortic valve disease in the whole population was 0.25% at baseline. Montelukast use was associated with a trend of decreased incidence of aortic stenosis, which did not reach statistical significance (Table 1). Table 1 Fully adjusted* hazard ratio (HR) with 95% confidence interval (95% CI) for aortic stenosis with montelukast (non-use was used as reference level) Several limitations of the present study should be acknowledged. The 3.5 years of exposure data available in the present study is relatively short given that aortic stenosis develops over a longer time. It can also not be excluded that previously exposed subjects may have been considered as unexposed, and that recently commenced montelukast treatment may not yet have affected the development of aortic stenosis. In addition, using the diagnosis code as outcome will not define the severity of aortic stenosis and will miss asymptomatic cases not seeking hospital care. The latter limitations can drive the association towards the null due to lower statistical power. Finally, in these national registry data, we are not able to adjust completely for all possible confounding factors. However, the most plausible confounders have been taken into account by adjustment for gender, age, socioeconomic status as well as cardiovascular and respiratory diagnoses and treatments. In summary, mechanistic studies have implicated the leukotriene pathway in aortic stenosis. Although the present study did not show a significant association of montelukast use with aortic stenosis, the results suggested a trend towards beneficial effects. However, the non-randomized, observational design of the present study means that no causality can be definitely attributed and that the association could be driven by unmeasured confounding. More importantly, the present study indicates a safety of anti-leukotriene drugs in the context of aortic stenosis. The latter finding is an important piece of information for the design of interventional studies targeting the leukotriene pathway in aortic stenosis.

Understanding the Molecular and Cellular Changes Behind Aortic Valve Stenosis

Morbidity from degenerative aortic valve disease (AVS) is increasing worldwide, concomitant with the ageing of the population and the growing consumption of high caloric and cholesterol diets of the western countries. Despite the increasing prevalence of AVS, with its high mortality and morbidity, studies on the molecular and cellular mechanisms underlying the onset of aortic valve degeneration have only advanced in the last 15 years. The result of this effort is now beginning to reveal several mechanisms with great therapeutic targeting potential that may alter the natural history of this progressive pathology. Indeed, the view of this disease has changed from being an unmodifiable degenerative disease to an active biological process regulated by highly conserved cellular pathways. The progression of AVS includes inflammation, angiogenesis and remodelling of the extracellular matrix leading to osteogenesis in the aortic valve and revealing many mechanisms and risk factors similar to atherosclerosis. Therefore statins and angiotensin II antagonists seemed promising treatment options; however, experimental results are still controversial. Nonetheless, valvular degeneration results in dramatic myocardial changes induced by chronic pressure overload such as left ventricular hypertrophy as well as other paramount myocardial extracellular changes. Currently, a strong impulse for future research to investigate the pathophysiological mechanisms and their modulation in order to prevent/delay the onset or progression of valve degeneration is needed. In the present review, we focused on the molecular and cellular mechanisms underlying degenerative AVS and its myocardial impact.

Prevalence of aortic valve abnormalities in the elderly: An echocardiographic study of a random population sample

Objectives. This study was undertaken to elucidate the prevalence of aortic valve abnormalities in the elderly.Background. The age of persons treated actively for valve disorders is increasing. More information is needed about the prevalence of aortic valve disease in old age.Methods. Randomly selected men and women in the age groups 75 to 76, 80 to 81 and 85 to 86 years (n = 501) participating in the Helsinki Ageing Study were studied with imaging and Doppler echocardiography. Additionally, 76 persons 55 to 71 year of age were included. The systolic aortic valve area was calculated by the continuity equation. The velocity ratio (peak velocity in the left ventricular outflow tract/peak velocity across the aortic valve) was a supplementary criterion for aortic stenosis. Valve regurgitation and cusp calcification were assessed visually.Results. Evaluation of the aortic valve was possible in 552 persons (96%). Mild calcification was found in 222 (40%) and severe calcification in 72 (13%). Two persons (0.4%) had an aortic valve prosthesis. Critical native valve stenosis (calculated aortic valve area ≤0.8 cm2and velocity ratio ≤0.35) was found in 12 persons (2.2%). Six of these were symptomatic and potentially eligible for valvular surgery. All persons with aortic valve stenosis were in the three oldest age groups. The prevalence of critical aortic valve stenosis was 2.9% (95% confidence Interval 1.4% to 5.1%) in the group 75 to 86 years of age. Aortic regurgitation, mostly mild, was found in 29% of the entire study cohort.Conclusions. Calcific aortic valve stenosis constitutes a significant health problem in the elderly. Only a minority of those with potentially operable aortic valve stenosis undergo surgery.