Comparison of the effects of lanthanum carbonate and calcium carbonate on the progression of cardiac valvular calcification after initiation of hemodialysis.

BACKGROUND: Although mineral metabolism disorder influences cardiac valvular calcification (CVC), few previous studies have examined the effects of non-calcium-containing and calcium-containing phosphate binders on CVC in maintenance hemodialysis patients. The aim of the present study was to compare the effects of lanthanum carbonate (LC) with calcium carbonate (CC) on the progression of CVC in patients who initiated maintenance hemodialysis and to investigate clinical factors related to CVC. METHODS: The current study included 50 subjects (mean age 65 years, 72% males) from our previous randomized controlled trial (LC group, N = 24; CC group, N = 26). CVC was evaluated as CVC score (CVCS) using echocardiography at baseline and 18 months after initiation of hemodialysis. We compared CVCS and the changes between the two groups. We also analyzed the associations between CVCS and any other clinical factors including arterial plaque score (PS) and serum phosphorus levels. RESULTS: Baseline characteristics of study participants including CVCS were almost comparable between the two groups. At 18 months, there were no significant differences in mineral metabolic markers or CVCS between the two groups, and CVCS were significantly correlated with PS (r = 0.39, p < 0.01). Furthermore, changes in CVCS were significantly correlated with average phosphorus levels (r = 0.36, p < 0.05), which were significantly higher in high serum phosphorus and high PS group compared to low serum phosphorus and low PS group (p < 0.05). CONCLUSIONS: In the present study, there were no significant differences between LC and CC with regard to progression of CVC. However, serum phosphorus levels and arterial plaque seem to be important for the progression and formation of CVC in hemodialysis patients.

Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors.

PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83). CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.

Ectopic calcification in diabetic vascular disease.

INTRODUCTION: Cardiovascular diseases represent over one-half of all deaths in both type 1 and type 2 diabetes mellitus. In diabetic patients, vascular calcifications are more frequently observed than in people without diabetes. In particular, elevated degrees of coronary artery and valvular calcifications are reported in populations with diabetes. AREAS COVERED: We will present and discuss findings from clinical and basic science studies that investigate the pathophysiological processes leading to exaggerated arterial/valve calcification in diabetic patients. We will also illustrate the likely effects of the current therapies on vascular calcification progression in diabetic patients. A special focus will be dedicated to the contribution of resident/circulating calcifying cells to the calcific processes observed under diabetic conditions. EXPERT OPINION: Interest in the topic of ectopic calcification in diabetic vascular disease is expanding and more knowledge is adding on its mechanisms and consequences. Importantly, new therapeutic targets are emerging, implying possible future chances to modulate vascular calcification for cardiovascular protection.

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo.

OBJECTIVE: Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. METHODS AND RESULTS: Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors. CONCLUSIONS: Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.

Diet-induced aortic valve disease in mice haploinsufficient for the Notch pathway effector RBPJK/CSL.

OBJECTIVE: Calcific aortic valve disease is similar to atherosclerosis in that both diseases result from chronic inflammation and endothelial dysfunction. Heterozygous NOTCH1 mutations have been associated to calcific aortic disease and a bicuspid aortic valve. We investigated whether mice with genetic inactivation of the Notch signaling pathway are prone to develop valve disease when exposed to a predisposing diet. METHODS AND RESULTS: Using Doppler echocardiography, histology, immunohistochemistry, quantitative gene expression analysis, and cell culture assays, we examined the effect of a hypercholesterolemic diet supplemented with vitamin D on mice heterozygous for null mutations in the Notch1 receptor or the effector transcription factor gene RBPJk. After 16 weeks on the hyperlipidemic diet, calcific aortic disease was detected in heterozygous RBPJk mice. Analysis of valve leaflets revealed macrophage infiltration, enhanced collagen deposition, proosteogenic protein expression, and calcification. Heterozygous null Notch1 mice displayed milder histopathologic changes and did not develop any significant hemodynamic disturbance. Valvular disease correlated with reduced expression of the Notch target gene Hey1 in valves of RBPJk heterozygous mice fed the hyperlipidemic diet. Consistent with the in vivo data, Notch signaling inhibition in porcine valve interstitial cells led to downregulation of HEY1 transcription, activation of osteogenic markers, and increased calcified nodule formation. CONCLUSIONS: We show that Notch signaling disruption via RBPJk heterozygous inactivation results in aortic valve disease. Notch1 heterozygous mice do not show functional impairment, suggesting that additional Notch receptors may be involved in aortic valve homeostasis and disease. Our data establish a genetic mouse model of calcific aortic valve disease and may help to identify a patient population with reduced valvular NOTCH signaling at risk for developing this disease.

[Cardiac valves calcifications in dialysis patients]. / Kalcifikacije srcanih zalistaka kod pacijenata na kronicnoj hemodijalizi.

Chronic kidney disease (CKD) patients, especially those with end-stage renal disease (ESRD), are at much higher risk of cardiovascular disease (CVD) than the general population. High serum phosphorus (P) level play important role in pathogenesis of cardiovascular calcifications and is a frequent and important cardiovascular risk factor in patients with CKD. We aimed to investigate the association of serum levels of C-reactive protein (CRP), parathyroid hormon (PTH). calcium phosphorus product (CaxP) with cardiac valves calcifications (VC) in patients on hemodialysis (HD). We investigated for VC using colour Doppler echocardiography. VC were considered present if mitral annular calcifications and/or aortic annular calcifications were visualized. We divided patients in two groups. VC negative group (VC-) were patients with absence of VC. Patients with presence of VC were VC positive (VC+). CRP mean levels in two samples were higher in VC+ group than in VC- group (17.0 vs 3.4mg/L) and (17.1 vs 4.0 mg/L) p<0.0001. CaxP mean level in both samples was higher in VC+ group than in VC- group, 4.8 vs 4.2 (p=0.0219) and 5.0 vs 4.3 (p=0.0078). We also made analysis of absolute highest levels of three samples of CRP (CRPmax) between groups. CRPmax was higher in VC+ group than in VC- group, 19.5 vs 9.7 mg/L, (p=0.0045). We made analysis of absolute higher levels of two samples of Ca x P (CaxPmax) between groups. CaxPmax was higher in VC+ group than in VC- group, 5.2 vs 4.4 (p=0.0014). We found cardiac valve calcifications in 40 percent of patients on hemodialysis. We found that patients with correlation between PTH level, CRP level, CaxP product and cardiac valve calcifications have higher serum levels of PTH and CRP. We also found that CaxP product is higher in patients with cardiac valve calcifications. We didn't find correlation between age, dialysis duration, BMI and cardiac valve calcifications. These findings support careful monitoring of calcium metabolisum in end stage renal disease to reduce valvular cacifications and the risk of cardiovascular disease.

Daptomycin for methicillin-resistant Staphylococcus epidermidis native-valve endocarditis: a case report.

Coagulase-negative staphylococci (CoNS) have been increasing in importance as a cause of native valve endocarditis (NVE). Most cases of NVE caused by CoNS are attributable to Staphylococcus epidermidis. NVE caused by CoNS acquired in a nosocomial setting may differ from cases acquired in the community in several ways. It may be associated with hemodialysis, the presence of a long-term indwelling central catheter or pacemaker, or a recent invasive procedure; nosocomial cases may have a higher rate of methicillin resistance among CoNS isolates, and so be more likely to be treated with vancomycin. Unfortunately, NVE caused by methicillin-resistant CoNS has been associated with significantly higher rates of persistent bacteremia and in-hospital mortality than methicillin-susceptible isolates. The poor outcomes in these cases point to the need for alternative therapies with potent activity against methicillin-resistant CoNS. In our medical center, a 76-year-old man presented with native-valve endocarditis and positive blood cultures for methicillin-resistant Staphylococcus epidermidis (MRSE). During each of three 6-week courses of treatment with vancomycin, blood cultures were negative, but they once again became positive for MRSE when vancomycin was discontinued. The minimum inhibitory concentration of the MRSE isolates for vancomycin remained stable at 2 microg/mL. Eventually, treatment with daptomycin was initiated (500 mg [7 mg/kg]) 3 times/week for 6 weeks. Over the following year, no positive cultures for MRSE were detected.

Oral calcium supplements do not affect the progression of aortic valve calcification or coronary artery calcification.

BACKGROUND: The use of oral calcium supplementation among the elderly for prevention and treatment of osteoporosis and osteopenia is increasing. The incidence of aortic valve disease and coronary artery disease also is increasing. No study thus far has been done to demonstrate whether this affects the progression of calcification in both the valves and vasculature. We sought to determine whether ingestion of oral calcium supplementation has an effect on aortic valve calcification (AVC) and coronary artery calcification (CAC). METHODS: We performed an independent assessment of AVC, CAC, and calcium supplementation among patients enrolled in the Epidemiology of Coronary Artery Calcification study who were >60 years of age and had baseline and 4-year follow-up AVC data. In this population-based study of Olmsted County (Minnesota) residents, AVC and CAC scores were determined prospectively by electron beam computed tomography. We evaluated baseline demographic data and analyzed whether those patients using calcium supplementation had a higher rate of progression of both AVC and CAC. RESULTS: We identified 257 patients (mean age, 67.8+/-5.2 years), 144 of whom were women. Twenty-five patients (all women) reported using calcium supplements. Analysis of the 144 women (25 taking calcium supplementation) showed there was no difference in the progression of AVC (mean difference in baseline and follow-up AVC score; no supplement versus supplement, 30+/-9 vs 39+/-28; P=.73) or CAC (mean difference in baseline and follow-up CAC score; no supplement vs supplement, 47+/-15 vs 112+/-22; P=.154). There were no significant differences between the 2 groups with regard to baseline AVC, serum calcium, renal function, diabetes, hypertension, cholesterol, or body mass index. CONCLUSION: In this community-based observational study with a 4-year follow-up, no significant increased progression of AVC or CAC was found in women taking oral calcium supplementation. Larger prospective, randomized studies are needed to confirm these findings.

Close association of vascular and valvular calcification and prognosis of patients on continuous ambulatory peritoneal dialysis.

In the present study, we examined the association between vascular and valvular calcification and the prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD). Data were collected from the records of patients introduced onto CAPD therapy during 1999 - 2006 at the Department of Nephrology, Saitama Medical University. At the start of CAPD, cardiac and vascular echography were used to examine 162 patients (average age: 56 +/- 5 years; 58 men, 104 women; 43 with and 119 without diabetes) for evaluation of vascular and valvular calcification. Both vascular and valvular calcification were found in 32 patients. Vascular calcification was found in 16, and valvular calcification in 11. Over 5 years, 11 patients suffered from cardiovascular disease (7 with stroke, 4 with myocardial infarction). All of these patients had vascular or valvular calcification at the start of CAPD therapy. We also used Cox hazard analysis to examine values for Ca, P, Ca x P, intact parathyroid hormone (iPTH), and lipids. None of these values were independent contributory factors for incidence of cardiovascular disease in patients on CAPD. These data suggest the importance of vascular and valvular echography to evaluate patients on CAPD, especially at the start of CAPD therapy. Vascular and valvular calcification are important factors for determining the prognosis of patients on CAPD.

[Heart involvement in systemic sclerosis]. / Atteinte cardiaque de la sclérodermie systémique.

Primary myocardial involvement is common in systemic sclerosis. Increasing evidence strongly suggests that this involvement is related to repeated focal ischemic injury causing irreversible myocardial fibrosis. The underlying mechanism appears to be microcirculatory impairment with abnormal vasoreactivity, with or without structural vascular abnormalities. Clinically evident cardiac involvement is recognized to be a poor prognostic factor. Pericardial involvement is frequent but usually asymptomatic. Conduction system abnormalities appear common but not serious, while arrhythmias may be life-threatening. No significant valvular involvement appears to be associated with systemic sclerosis. Treatment for myocardial involvement includes long-term systematic administration of calcium channel blockers and possibly angiotensin-converting enzyme inhibitors, frequently given at high dosage.

[Significance of serum calcium and phosphorus control for the cardiac function in patients with long term hemodialysis].

We evaluated how serum calcium and phosphorus will effect a cardiomegaly of hemodialysis patients. The cardiac valve of hemodialysis patients have a high incidence of calcification. Forty four percent of mitral valve and seventy five percent of aortic valve occurred the calcification, and the progress of calcification involve with increasing LVMI. The consequence of this results was that we consider prevent calcification is important to inhibiting factor of cardiomegaly, but serum calcium and phosphorus wasn't effect a cardiomegaly. On the other hand, we detected a significant negative correlation between serum calcium and LVMI (P = 0.0008) and a significant positive correlation between serum phosphorus and LVMI (P = 0.0105) . Consequently we thought that to control the serum phosphorus is important factor to inhibit the cardiomegaly.

Idiopathic ventricular arrhythmia arising from the mitral annulus: a distinct subgroup of idiopathic ventricular arrhythmias.

OBJECTIVES: We sought to clarify the prevalence and characteristics of idiopathic ventricular tachycardia or premature ventricular contraction originating from the mitral annulus (MAVT/PVC). BACKGROUND: Recent case reports have presented patients with MAVT/PVC. METHODS: Electrocardiographic (ECG) characteristics and the results of electrophysiologic investigation and radiofrequency catheter ablation (RFCA) were analyzed in 352 patients with symptomatic idiopathic ventricular tachycardia (IVT)/premature ventricular contraction (PVC). RESULTS: Nineteen cases of IVT/PVC (5%) represented MAVT/PVC. Of these, 11 (58%) originated from the anterolateral portion of the mitral annulus (AL-MAVT/PVC), and 2 (11%) arose from the posterior portion (Pos-MAVT/PVC). The remaining six cases of MAVT/PVC (31%) had posteroseptal origin (PS-MAVT/PVC). In all patients, an S-wave was present in lead V(6). The QRS polarity in inferior leads and leads I and aVL was useful for differentiating AL-MAVT/PVC from Pos-MAVT/PVC or PS-MAVT/PVC. The Pos-MAVT/PVC had an Rs pattern in lead I and an R pattern in lead V(1), whereas PS-MAVT/PVC invariably had an R pattern in lead I and a negative QRS component in lead V(1). The AL-MAVT/PVC and Pos-MAVT/PVC showed a longer QRS duration than the PS-MAVT/PVC (p < 0.001), and all had late-phase "notching" of the QRS complex in inferior leads. In all patients, RFCA eliminated MAVT/PVC, with no recurrences during follow-up for 21 +/- 15 months. CONCLUSIONS: Mitral annular VT/PVC is a rare but distinct subgroup of IVT/PVC. MAVT/PVC origin could be determined by ECG analysis. The AL and PS sites of the MA were preferential.

Histopathogenesis of early-stage mitral annular calcification.

Mitral annular calcification (MAC) is a common condition in elderly subjects that sometimes causes degenerative mitral valvular diseases. To investigate the early histopathogenesis of MAC, we examined 180 consecutive autopsies of elderly subjects. After a macroscopic and radiological examination, 5-mm-thick serial tissue blocks obtained from the mitral annulus were examined in all MAC cases. Five cases without MAC were also studied using histology, immunostaining, electron microscopy, analytical electron microscopy and the TUNEL method. The incidence of MAC in females (23%) was higher than that in males (15%). Most MAC was located at the posterior cusp (91%). The mitral annulus showed signs of microscopic calcification and lipid-deposition in some degenerated areas in all of the cases without MAC. The interstitial cells were positive for vimentin and partially positive for smooth muscle actin, indicating the myofibroblastic differentiation. Ultrastructural studies showed an abundance of cellular degradation products and foci of calcium- and phosphorus-deposition on these products in the interstitium. Several interstitial cells tested positive for both single-stranded DNA immunostaining and the TUNEL reaction. In conclusion, the microscopic calcification of mitral annulus is an early stage of MAC and caused by calcium-deposition on cellular degradation products, probably released from apoptotic or necrotic interstitial cells.

Warfarin and herbal products interaction causing prosthetic aortic valve thrombosis presenting as acute myocardial infarction.

Myocardial infarction (MI) due to coronary artery embolization is a rare and potentially lethal complication of prosthetic heart valve thrombosis. A 58-year-old man in whom the aortic valve was replaced with a bileaflet mechanical valve presented with an acute anterior MI. Valvular dysfunction was detected by physical examination, and confirmed by two-dimensional echocardiography and cinefluoroscopy. Coronary angiography disclosed embolization of the left anterior descending artery. Thrombotic encroachment of one of the prosthetic valve leaflets was found at reoperation. Failure to achieve adequate anticoagulation was likely due to an interaction between warfarin and herbal products. These findings have significant implications regarding the diagnosis and treatment of acute MI in patients with left-sided prosthetic heart valves, and emphasizes the importance of appropriate anticoagulation in this setting.

[Transesophageal echocardiographic evaluation of tricuspid endocarditis from implanted pacemaker: description of two cases]. / Valutazione con ecocardiografia transesofagea dell'endocardite tricuspidale da impianto di pacemaker: descrizione di due casi.

Two cases of tricuspid valve endocarditis due to staphylococcus epidermidis have been examined in patients with permanent transvenous pacemaker. While transthoracic echocardiography was unable to detect any tricuspidal abnormalities, large vegetations located on the tricuspidal leaflets and the electrocatheter were detected by transesophageal echocardiography. Both cases required surgical removal of the electrostimulation system and valve toilet.

Slowing of mitral valve annular calcium in systemic hypertension by nifedipine and comparisons with enalapril and atenolol.

Mitral annular calcium (MAC) is a condition that often occurs in patients with systemic hypertension. To evaluate the effectiveness of nifedipine in preventing MAC, 223 patients with systemic hypertension of recent onset and without MAC were selected and randomly enrolled in 3 groups: group 1 (76 patients) received nifedipine; group 2 (72 patients) received enalapril; and group 3 (75 patients) received atenolol. After 5 years, these treatments significantly reduced systolic (p < 0.001) and diastolic (p < 0.05) blood pressure (BP) in 3 treated groups. M-mode echocardiography revealed MAC only in 2 patients in the nifedipine group (2.6%), in 13 in the enalapril group (18%) and in 15 in the atenolol group (20%). The degree of MAC was mild (< 5 mm) in the 2 patients in group 1, in 5 of the 13 in group 2, and in 6 of the 15 in the group 3, whereas it was severe (> 5 mm) in the remaining 8 in the enalapril group and in the other 9 in the atenolol group. There was also a significant correlation in the degree of MAC, left atrial enlargement and mitral regurgitation. In addition, atrial fibrillation and atrioventricular conduction defects were associated with severe MAC. These results indicate that nifedipine is an effective drug both in the long-term management of systemic hypertension and in preventing or delaying MAC.

Myocardial texture and cardiac calcification in uremia.

Seventy patients with advanced chronic renal failure were examined by 2D echocardiography in an effort to determine the prevalence of changes in myocardial texture and of valvular calcification. Changes in myocardial texture may be due to calcium deposition in the myocardium, the relationship between changes in myocardial texture and factors that may enhance myocardial calcification (blood levels of parathyroid hormone, PTH, and calcium-phosphorus product) were also evaluated. Myocardial texture was abnormal in 36 patients. In 68 patients, structural calcification could be assessed; a high degree of calcification was found. No correlation was found between either the echocardiographic parameter and blood levels of PTH or calcium-phosphorus product. We conclude that myocardial textural changes and intracardiac calcification are common in chronic renal failure and that these abnormalities do not correlate with blood PTH levels or calcium-phosphorus product.