Valvular Heart Disease Patients Research Articles

Exercise stress echocardiography in patients with valvular heart disease.

Stress echocardiography is recommended for the assessment of asymptomatic patients with severe valvular heart disease (VHD) when there is discrepancy between symptoms and resting markers of severity. The aim of this study is to determine the prognostic value of exercise stress echocardiography in patients with common valve lesions. One hundred and fifteen patients with VHD (aortic stenosis (n=28); aortic regurgitation (n=35); mitral regurgitation, (n=26); mitral stenosis (n=26)), and age- and sex-matched controls (n=39) with normal ejection fraction underwent exercise stress echocardiography. The primary endpoint was a composite of death or hospitalization for heart failure. Asymptomatic VHD patients had lower exercise capacity than controls and 37% of patients achieved <85% of their predicted metabolic equivalents (METS). There were three deaths and four hospital admissions, and 24 patients underwent surgery during follow-up. An abnormal stress echocardiogram (METS <5, blood pressure rise <20 mmHg, or pulmonary artery pressure post exercise >60 mmHg) was associated with an increased risk of death or hospital admission (14% vs 1%, P<0.0001). The assessment of contractile reserve did not offer additional predictive value. In conclusion, an abnormal stress echocardiogram is associated with death and hospitalization with heart failure at 2 years. Stress echocardiography should be considered as part of the routine follow-up of all asymptomatic patients with VHD.

VKORC1 -1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose.

In this study, we investigated two VKORC1 gene polymorphisms, -1639G/A and 1173C/T, for effects on warfarin maintenance dosage in valvular heart disease (VHD) patients after cardiac valve replacement (CVR). A total of 219 VHD patients receiving warfarin therapy after CVR surgery were recruited to this study between June 2010 and December 2013. Basic clinical data, prothrombin time, warfarin maintenance dose, and blood samples were collected from all patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were used to analyze the VKORC1 -1639G/A and 1173C/T polymorphisms. SPSS version 19.0 software was used for statistical analysis of the data. Patients with either the AG+or GG genotype (n=32) of the VKORC1 -1639G/A polymorphism required a significantly higher warfarin dose compared to patients with the AA genotype (n=187) (4.36±1.03 mg/day vs. 2.95±0.94 mg/day; p<0.001). Similarly, patients carrying the CT genotype (n=28) of the VKORC1 1173C/T polymorphism also required a significantly higher warfarin dose compared to those with the TT genotype (n=191) (4.19±0.99 mg/day vs. 3.00±0.94 mg/day; p<0.001). Linear regression analysis showed that gender, age, weight, and VKORC1 -1639G/A and 1173C/T polymorphisms were correlated with individual differences in warfarin maintenance dose (all p<0.05). We present evidence that the two VKORC1 polymorphisms, -1639G/A and 1173C/T, are key genetic factors influencing individual differences in warfarin maintenance dose in VHD patients who underwent CVR. Gender, age, and weight also independently correlated with warfarin maintenance dose.

The Influence of Frailty on Outcomes in Cardiovascular Disease

Physicians practicing in the modern era are confronted with an ever aging and comorbid population. A working knowledge of the principles of frailty and its application to distinct medical conditions can help the clinician tailor recommendations to optimize both patient-centered goals and traditional outcomes. In this article, we will define frailty and synthesize the recent evidence on its role in affecting outcomes across the spectrum of cardiovascular disease (CVD). Frailty is defined as a state of susceptibility in which a person has decreased physical reserve that leads to a greater likelihood of an adverse outcome when a stressor is applied. The concept of frailty came to prominence after a seminal publication by Fried et al,. in which frailty was described as low overall physical activity level, unintentional weight loss, slow walking speed, fatigue, and loss of physical strength.1,2 Later works broadened this definition to include a variety of other factors, ie, comorbid medical conditions, loss of independence for activities of daily living, low albumin levels, and cognitive impairments.3,4 The pathophysiologic basis of frailty involves an interplay of aging-associated biologic changes and long-term “wear and tear” leading to subclinical organ dysfunction.5,6 The application of a stressor (in the form of an illness) makes “subclinical” disease become “clinical” and may result serious adverse outcomes (Figure).7 Figure Two of the pathways leading to frailty. The baseline biological changes associated with aging combined with subclinical disease from long-term “wear and tear” lead to the signs and symptoms of the frailty phenotype. (Adapted with permission ... The overall prevalence of frailty in adults age 65 years and older has been estimated at approximately 10%. However, in patients with significant CVD, the prevalence may be as high as 60%.8,9 In 2009, Afilalo et al10 conducted a systematic review evaluating the risk of concomitant frailty and CVD. The study pooled 54 250 elderly patients from 9 studies and demonstrated an increased risk of death in those with concomitant frailty and CVD with an adjusted odds ratio ranging from 1.6 to 4.0 across the evaluated studies. The frail phenotype is even more pervasive in valvular heart disease patients, particularly in calcific aortic stenosis (primarily seen in patients older than 70 years of age). In high risk transcatheter aortic valve implantation (TAVI) patients with calcific aortic stenosis, the prevalence of frailty was as high as 86%.11

Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation

ObjectiveVascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. MethodsMicroparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. ResultsCompared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. ConclusionsOur data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively.

36 Direct Measurement of Cardiac Compensation in Valvular Heart Disease

<h3>Purpose</h3> The natural history of valvular heart disease (VHD) suggests that the heart initially adapts to compensate for valve lesions and thereby maintain physiological function. When these compensatory mechanisms become exhausted, cardiac decompensation commences. We tested the hypothesis that all VHD patients with normal exercise capacity are in the compensatory phase with no symptoms and normal cardiac reserve. <h3>Methods</h3> Unselected consecutive male patients with VHD performed cardiopulmonary exercise (CPX) testing with non-invasive central haemodynamic measurements during symptom-limited treadmill exercise. Exercise capacity was represented by peak oxygen consumption (VO_2max) and cardiac pumping capability by peak exercise cardiac power output (CPO_max). Data are given as mean±SD. <h3>Results</h3> Of the entire VHD patient cohort (n = 215), 81.4% (n = 175) had VO_2max which were within or above the reference range of healthy male sedentary controls (n = 101). This is shown in Figure 1A where individual patient VO_2max is expressed as a percentage of the average VO_2max of age- and sex-matched controls. These 175 patients with normal VO_2max had a mean age of 63.1 ± 14.0 years, and consisted of 98 (56%) who were asymptomatic (NYHA class I) and 77 (44%) who were discordantly symptomatic in NYHA II+ (.001). As shown in Figure 1B, 117 patients (66.9%) had CPO_max within the normal range, of whom 80 (45.7%) were asymptomatic, but 37 (21.1%) were in NYHA II+ despite having normal VO_2max and CPO_max (.001). Conversely, 58 (33.1%) had CPO_max below the normal range, and yet 18 (10.3%) of these were discordantly still in NYHA I (P &lt; 0.001). These patients were classified asymptomatic by their responsible clinicians but our results revealed they had early, objective evidence of cardiac decompensation. <h3>Conclusions</h3> This investigation demonstrates that it is now possible to directly and objectively measure whether patients are in the compensated or decompensated phases of VHD. There were discrepancies between subjective symptomatic statuses and objectively measured cardiac and physical functional statuses. The possibility to determine whether patients are in the compensatory phase or not, might help in the management of difficult VHD cases.

Abstract 628: Circulating Microparticles From Patients With Valvular Heart Disease and Cardiac Surgery Inhibit Endothelium Dependent Vasodilation.

Objective: Circulating microparticles (MPs) from some diseases play important roles on inflammation, coagulation and vascular injury. The vascular function is quite important for maintaining the circulation after cardiac surgery. However, the impact of MPs generated from valvular heart disease (VHD) and cardiac surgery on vascular function remains unknown. The present study is to investigate the impact of such MPs on vasodilation. Methods: MPs were isolated from age-match healthy subjects and patients with VHD before and at 12 h, 72 h after cardiac surgery. Effects of MPs on vasodilation of mice aorta, the phosphorylation and expression of Akt, protein kinase C βII (PKC-βII), p70S6K, endothelial nitric oxide synthase (eNOS) and caveolin-1, the association of eNOS with heat shock protein 90 (HSP90), generation of nitric oxide (NO) and superoxide anion (O2•–) of human umbilical vein endothelial cells (HUVECs) were determined. Results: Compared with MPs from healthy subjects, MPs from VHD patients before cardiac surgery can impair endothelium-dependent vasodilation, inhibit phosphorylation of Akt and eNOS, enhance expression of caveolin-1, and activation of PKC-βII, p70S6K, and reduced association of HSP90 with eNOS, decrease NO production and increase O2•– generation. Those effects were even stronger when treated with MPs from post- cardiac surgery. Conclusion: Our data demonstrated that circulating MPs generated before and after cardiac surgery in VHD patients contributed to endothelial dysfunction by inhibiting and uncoupling of eNOS activity. Circulating MPs may be a potential therapeutic target for maintenance of vascular function post-cardiac surgery.

Prevalence and significance of two major inherited thrombophilias in infective endocarditis.

The pathogenesis of infective endocarditis (IE) involves activation of the haemostasis system at the site of endocardial defects. Whether prothrombotic conditions are associated with IE by enhancing early vegetation formation is unknown. In this study, we assess the prevalence and clinical significance of two major conditions associated with thrombophilia in patients with IE. Mutations G20210A of the prothrombin (PTH) gene and G1691A of factor V (FV Leiden) gene were studied by means of allele-specific polymerase chain reaction in 203 IE patients, 175 valvular heart disease (VHD) patients and 200 blood donors (BD). IE patients show higher cumulative frequencies of mutated alleles of PTH and FV Leiden [6.4 vs 3.25 %; OR 2.03 (95 % CI 0.97-3.66); p = 0.047] compared to BD, but not VHD. Device-related IE is enriched with FV Leiden, and prosthetic valve IE with PTH mutations (allele frequency 8.3 vs 2.2 % in native valve IE; p = 0.021). Vegetation size and embolic complications are not influenced by the examined thrombophilias. A trend for a higher mortality was observed in IE patients with any of the two thrombophilias studied. Our data do not support a role for factor V Leiden and G20210A prothrombin gene mutations in the susceptibility to IE. Whether any of these genetic polymorphisms play a role in a specific subtype of IE needs to be re-examined in larger studies.

EuroSCORE models in a cohort of patients with valvular heart disease and a high prevalence of rheumatic fever submitted to surgical procedures.

ObjectivesEpidemiological differences can be found between Brazilian and European valvular heart disease patients. The prevalence of heart valve diseases due to rheumatic disease is significantly higher in the Brazilian compared with the European population. Therefore, they could have different risks during and after cardiac surgery. The aim of this study was to evaluate the applicability of the additive and logistic EuroSCORE and EuroSCORE II in a cohort of high-risk patients with valvular heart disease of predominantly rheumatic aetiology submitted to surgery.MethodsBetween 1 February and 30 December 2009, 540 consecutive patients scheduled for valvular heart surgery were included in this study. In this set of patients, we examined the performance of the additive, logistic, and EuroSCORE II models for predicting in-hospital mortality. Calibration of each model was assessed by comparing predicted and observed in-hospital mortality and by the goodness of fit of the Hosmer-Lemeshow chi-square test. Discrimination performance of the model was evaluated with the receiver operating characteristic (ROC) curve analysis.ResultsThe mean age was 56 ± 16 years, 50.6% were female, and the mortality rate was 16.0% (6.0% in elective surgery and 34.0% in emergency/urgency surgery). Mortality rates were estimated according to the additive and logistic EuroSCORE and EuroSCORE II at 6.1%, 8.7%, and 4.3%, respectively. The AUC was 0.76 (95% confidence interval [95% CI] 0.70–0.81) for the additive EuroSCORE, 0.76 (95% CI 0.70–0.81) for the logistic EuroSCORE and 0.81 (95% CI 0.76–0.86) for EuroSCORE II. Hosmer-Lemeshow goodness-of-fit statistics were P = 0.52, P = 0.07, and P = 0.12 for additive, logistic EuroSCORE, and EuroSCORE II.ConclusionsIn this cohort of Brazilian patients with valvular heart disease submitted to surgical procedure, the EuroSCORE models had a good discriminatory capacity; however, the calibration was compromised because of an underestimation of the mortality rate.

Th17-Related Cytokines in Systemic Lupus Erythematosus Patients with Dilated Cardiomyopathies: A Possible Linkage to Parvovirus B19 Infection

Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively). Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01). Five (62.5%) of DCM patients had detectable anti-B19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients.

Prevalence of Coronary Artery Disease in Patients of Rheumatic Heart Disease

Background: Few studies have focused on the prevalence of CAD in RHD. Coronary angiography should be routinely done in patients of valvular heart disease prior to surgery, especially in patients above 40 years of age. Overlooking CAD can lead to complications and poor results in post-operative period of valvular surgery. Clinical symptoms are common in both CAD and RHD. Indian studies by V. Jacob Jose and Satya N Gupta have studied this aspect in detail and their results are quite different from Western literature. Material & Methods: This study was conducted in all patients of valvular heart disease (RHD) above 40 years of age. Apart from basic investigations and echocardiography, coronary angiogram was done in all patients and were evaluated for presence of CAD (significant ≥ 50% or insignificant). They were also evaluated for SVD/DVD or TVD and risk factors (hypertension, diabetes mellitus, dyslipidemia) and symptoms especially angina were correlated to the presence of CAD. Results: Out of the 100 patients of RHD from Jan 2008- June 2009 at PGIMER, Chandigarh, 38 were males and 62 were females. 12 had significant CAD, while 9 had non-significant CAD. Mean age for significant CAD was 52.58 years. Age distribution was statistically significant in the 51-60 year age group. 66 patients had mitral valve disease, 31 had combined mitral and aortic valve disease, while 3 had predominantly aortic valve disease. Angina was the only symptom which correlated with presence of CAD especially in aortic valve disease group, but p value was non-significant. In risk factor category, only hypertension and total cholesterol were statistically significant with CAD. Conclusion: Prevalence of significant CAD was 12%. 5 patients had SVD, 4 had DVD & 3 had TVD. 2 patients with MS, 4 with MS/MR, 4 with MV+AV and 2 with predominant aortic valve group had significant CAD. Angina was not found to be a useful clinical symptom to predict CAD. Hypertension and total cholesterol were the only risk factors which could be correlated with CAD in RHD group. Keywords: Coronary artery disease, valvular heart disease. Read more →

Abstract 17912: Importance of Acute Hemodynamic Effects of Inhaled Nitric Oxide in Optimization of Heart Failure Treatment in Patients with Pulmonary Hypertension due to Left Heart Disease

Background: Pulmonary hypertension (PH) due to left heart disease (LHD) is a major category of the disorder. We have recently reported that elevated pulmonary vascular resistance (PVR) in patients with post-capillary PH (pc-PH: defined as mean pulmonary arterial pressure (mPAP)≥25mmHg and pulmonary capillary wedge pressure (PCWP)&gt;15mmHg) is associated with poor prognosis compared with those with no PH or pc-PH without elevated PVR. Although new treatment is required for targeting pulmonary vascular disease (PVD), thereis a concern about raising PCWP. In this study, we thus examined acute hemodynamic effects of inhaled nitric oxide (iNO) in patients with PH due to LHD and whether optimal heart failure (HF) treatment ameliorates pc-PH. Methods: We examined 60 consecutive pc-PH patients with chronic heart failure (63±14[SD] years, M/F 38/22, NYHA≥2) who underwent acute vasoreactivity test by iNO (40 ppm for 10 min) under right heart catheterization at our hospital from June 2011 to May 2014. Among them, 25 had valvular heart disease (VHD) and 35 had non-VHD. PVD (defined as PVR&gt; 240dynes/s/cm -5 ) was noted in 18. We also evaluated right ventricular systolic pressure (RVSP) by echocardiography after optimization of HF treatment such as medications and valvular surgery. Results: iNO significantly decreased mPAP (-1.7±0.5 mmHg; P&lt;0.01) and PVR (-66 ±14dyne/s/cm -5 , P&lt;0.01) without altering cardiac output. iNO significantly increased PCWP (1.3±0.5 mmHg, P=0.01) only in non-VHD patients, while it significantly increased mean arterial pressure and systemic vascular resistance in VHD patients than in non-VHD patients (both P&lt;0.05). Pc-PH patients with PVD were re-classified as having pc-PH without PVD in 9 and no PH in 1. Eight patients remained pc-PH with PVD. After the optimal medical treatment for 7.6 months, RVSP was significantly decreased in both non-VHD and VHD patient (-8±3mmHg, P=0.04, -19±8mmHg, P=0.01, respectively). However, in non-VHD group, significant reduction in RVSP was noted only in pc-PH patients without PVD (-8±3mmHg, P=0.03). Conclusions: These results indicate that elevated PVR in patients with pc-PH and non-VHD could be a novel therapeutic indication for NO-related pulmonary vasodilators in the current practice of HF.

High density lipoprotein from patients with valvular heart disease uncouples endothelial nitric oxide synthase

Normal high density lipoprotein (HDL) protects vascular function; however these protective effects of HDL may absent in valvular heart disease (VHD). Because vascular function plays an important role in maintaining the circulation post-cardiac surgery and some patients are difficult to stabilize, we hypothesized that a deleterious vascular effect of HDL may contribute to vascular dysfunction in VHD patients following surgery. HDL was isolated from age-match 28 healthy subjects and 84 patients with VHD and during cardiac surgery. HDL pro-inflammation index was measured and the effects of HDL on vasodilation, protein interaction, generation of nitric oxide (NO) and superoxide were determined. Patients with VHD received either simvastatin (20mg/d) or routine medications, and endothelial effects of HDL were characterized. HDL inflammation index significantly increased in VHD patients and post-cardiac surgery. HDL from VHD patients and post-cardiac surgery significantly impaired endothelium-dependent vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS) phosphorylation at S1177, eNOS associated with heat shock protein 90 (HSP90), NO production and increased eNOS phosphorylation at T495 and superoxide generation. Simvastatin therapy partially reduced HDL inflammation index, improved the capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and superoxide generation, and improved endothelium-dependent vasodilation. Our data demonstrated that HDL from VHD patients and cardiac surgery contributed to endothelial dysfunction through uncoupling of eNOS. This deleterious effect can be reversed by simvastatin, which improves the vasoprotective effects of HDL. Targeting HDL may be a therapeutic strategy for maintaining vascular function and improving the outcomes post-cardiac surgery.

Pregnancy complicated by valvular heart disease: an update.

Cardiovascular disease complicates ≈1% to 3% of all pregnancies and is responsible for 10% to 15% of maternal mortality. Although its prevalence is considered relatively low in pregnant women, heart disease is the most common cause of maternal mortality. Because more women with congenital or

Abstract 549: High-Density Lipoprotein from Valvular Heart Disease and Cardiac Surgery Uncouples Endothelial Nitric Oxide Synthase Activity to Impair Vasodilation

Background: The vascular effects of high density lipoprotein (HDL) may be highly heterogeneous. Normal HDL protects vascular function. Vascular function plays an important role in maintaining the circulation stable post-cardiac surgery. The vascular effects of HDL in valvular heart disease (VHD) and cardiac surgery remain unknown. The present study is to determine the vascular effects of HDL from VHD and cardiac surgery. Methods: HDL was isolated from healthy subjects and patients with VHD and during cardiac surgery. HDL inflammation index was measured by cell free assay. Effects of HDL on vasodilation, protein interaction, generation of nitric oxide (NO) and superoxide anion (O 2 ·– ) were determined. Results: HDL inflammation index significantly increased in VHD patients and post-cardiac surgery. HDL from VHD patients and post-cardiac surgery significantly impaired endothelium-dependent vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS) phosphorylation, eNOS associated with heat shock protein 90, NO production and increased O 2 ·– generation. Conclusions: The vasoprotective effects of HDL from VHD patients and cardiac surgery is impaired by uncoupled eNOS activity. HDL may be a therapeutic target for maintaining the stable circulation in post-cardiac surgery.

Investigating the Effect of Inflammation on Atrial Fibrillation Occurrence by Measuring Highly Sensitive C-reactive Protein (hs-CRP)

Introduction: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to reduce the clinical burden of AF by modulating inflammatory pathways. Materials and Methods: In a case-control study, 50 patients with atrial fibrillation (AF) with different etiologies and 50 patients with sinus rhythm and similar bases were selected. Sampling for highly sensitive c-reactive (hs-CRP) was done on the patients presenting with AF to the Ghaem hospital between October 2006 and June 2007. Results: Mean age of the patients was 62 years with maximum of 90 and minimum of 36 and standard deviation of 13.80. The most frequent age group was 71-80years. Fifty-four percent of patients were male and 46% were female. Mean serum hs-CRP levels in AF patients with hypertension (HTN) ,Ischemic heart disease(IHD), Valvular heart disease (VHD), HTN+IHD and hyperthyroidism were 8.10, 9.40, 8.68, 10.16 and 5.98 mg/Lit; respectively. There was significant difference between hs-CRP levels in hypertensive patients in the two groups (P=0.010). Similar results were observed in IHD patients, VHD patients and HTN+IHD patients in two groups (P=0.015, P=0.037, P=0.000). Conclusion: In addition to some risk factors like baseline cardiac diseases, aging, thyrotoxicosis, pulmonary embolism, pneumonia and cardiac surgery, there also appears to be consistent links between hs-CRP, a marker of inflammation, and the pathogenesis of AF.

Possible Involvement of Fibrocytes in Atrial Fibrosis in Patients With Chronic Atrial Fibrillation

Chronic atrial fibrillation (AF) is characterized by a remodeling process with prominent atrial fibrosis. Fibrocytes, a bone marrow-derived population of fibroblast-like cells, have been placed at the center of a number of fibrosing conditions. The purpose of this study was to evaluate the contribution of fibrocytes to atrial fibrosis in patients with chronic AF and the possible mechanisms. We enrolled 22 consecutive valvular heart disease patients with chronic AF (>6 months: CAF group) and 15 valvular heart disease patients in sinus rhythm served as controls (SR group). Left atrial tissue samples were obtained during cardiac surgery. The infiltration of fibrocytes into the atrial interstitium was observed by confocal microscopy. The number of atrial fibrocytes was approximately three-fold higher in the CAF group compared with the SR controls, and positively correlated with both the atrial collagen volume fraction (r=0.713; P=0.0002) and the left atrial volume index (r=0.631; P=0.002). In the peripheral blood samples collected before the operation, approximately 2.5-fold higher percentage of circulating fibrocytes was identified in the CAF group. These fibrocytes showed a stronger proliferative capacity (≍2.5-fold) and higher level expression of collagen I and α-SMA (≍2-fold and 4-fold, respectively) compared with the SR controls. The results suggested that fibrocytes may be involved in atrial fibrosis in chronic AF through enhanced profibrotic characteristics.

Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation

The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients.

ESC Working Group on Valvular Heart Disease Position Paper--heart valve clinics: organization, structure, and experiences

With an increasing prevalence of patients with valvular heart disease (VHD), a dedicated management approach is needed. The challenges encountered are manifold and include appropriate diagnosis and quantification of valve lesion, organization of adequate follow-up, and making the right management decisions, in particular with regard to the timing and choice of interventions. Data from the Euro Heart Survey have shown a substantial discrepancy between guidelines and clinical practice in the field of VHD and many patients are denied surgery despite having clear indications. The concept of heart valve clinics (HVCs) is increasingly recognized as the way to proceed. At the same time, very few centres have developed such expertise, indicating that specific recommendations for the initial development and subsequent operating requirements of an HVC are needed. The aim of this position paper is to provide insights into the rationale, organization, structure, and expertise needed to establish and operate an HVC. Although the main goal is to improve the clinical management of patients with VHD, the impact of HVCs on education is of particular importance: larger patient volumes foster the required expertise among more senior physicians but are also fundamental for training new cardiologists, medical students, and nurses. Additional benefits arise from research opportunities resulting from such an organized structure and the delivery of standardized care protocols. The growing volume of patients with VHD, their changing characteristics, and the growing technological opportunities of refined diagnosis and treatment in addition to the potential dismal prognosis if overlooked mandate specialized evaluation and care by dedicated physicians working in a specialized environment that is called the HVC.

The Turkish registry of heart valve disease

Valvular heart diseases (VHD) occur frequently in Turkey. However, epidemiological studies of VHD have not been completed until now. The aim of this study is to identify the VHD type, clinical, laboratory characteristics, and treatment methods among VHD patients in Turkey. The study was conducted prospectively between June 2009 and June 2011 at 42 centers, and included patients with native VHDs, infective endocarditis, and/or previous valve interventions. All medical data from 1300 patients were recorded. Mean age was 57±18 years and the female/male ratio was 1.5. VHD was native in 84% of patients, 15% had previous interventions, and 1% had infective endocarditis. Among the native VHDs, mitral regurgitation was the most frequent lesion (43%), followed by multiple VHDs (32%). Degenerative etiology (86%) was more frequent in aortic VHD, and rheumatic origin was the main cause in all VHDs. While the prevalence of aortic stenosis increased with age, mitral stenosis decreased with patient age. The most frequent symptom was shortness of breath (73%). Clinical and echocardiographic examinations (54%) were mostly used as diagnostic techniques for determining treatment course. Percutaneous mitral balloon valvuloplasty (PMBV) was performed in 76% of the patients with mitral stenosis and mechanical prosthetic valve replacement was performed in 74% of the patients with other lesions. This study showed that the main cause of VHD is rheumatic fever. Mitral regurgitation and multiple valvular lesions are the most frequent VHDs in Turkey. PMBV and mechanical prosthetic valve replacement are the preferred treatment methods for VHD.

Calcium- and integrin-binding protein-1 and calcineurin are upregulated in the right atrial myocardium of patients with atrial fibrillation

The aim of this study was to determine whether altered expression and distribution of calcium- and integrin-binding protein-1 (CIB1) is involved in the pathogenesis of different types of patients with atrial fibrillation (AF) associated with valvular heart disease (VHD). Right atrial specimens obtained from 65 patients undergoing valve replacement surgery were divided into three groups: sinus rhythm group (n= 24), paroxysmal atrial fibrillation group (PaAF; n= 10), and persistent atrial fibrillation group (PeAF; AF lasting >6 month; n= 31). The expression levels of mRNA and protein content for CIB1, calcineurin B, calcineurin A, and Na(+)-Ca(2+) exchanger-1 (NCX1) were measured. We also measured the combination of CIB1 with calcineurin B, L-type Ca(2+) channel, and NCX1 using immunoprecipitation. Expression of mRNA and protein content of CIB1, calcineurin B, calcineurin A, and NCX1 was increased in the AF group. Calcium- and integrin-binding protein-1 interacted with calcineurin B and L-type Ca(2+) channel. Surprisingly, CIB1 also combined with NCX1. The CIB1 and calcineurin expression was increased in AF atrial tissue and was related to the type of AF. This finding suggests that CIB1 may be involved in the pathogenesis of AF in VHD patients.