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Significance of commissural calcification on outcome of mitral balloon valvotomy.

OBJECTIVE: To evaluate the significance of commissural calcification, identified by transthoracic echocardiography, on the haemodynamic and symptomatic outcome of mitral balloon valvotomy. METHODS: Commissural calcification was graded from 0-4 using parasternal short axis transthoracic views. The morphology of the mitral valve was also assessed using the Massachusetts General Hospital echo score. SETTING: A tertiary cardiac centre in Scotland. PATIENTS: 300 patients were studied, 85 retrospectively and 215 prospectively. Mean (SD) age was 59.8 (12.7) years, range 13 to 87; 30% had been judged unsuitable for surgery. Median echo score was 6.8 (3.0), range 2-16. MAIN OUTCOME MEASURES: Immediate increase in mitral valve area and in New York Heart Association functional class 1-3 months after balloon valvotomy. RESULTS: On univariate and multivariate analysis, commissural calcification grade was a significant predictor of achieving a mitral valve area of > 1.50 cm(2) without severe mitral reflux. Its influence was greatest in patients with an echo score </= 8: those with commissural calcification grade 0/1 had significantly greater improvement in valve area and symptom status than those with grade 2/3; the proportions of patients achieving a final valve area of > 1.50 cm(2) were 67% and 46%, respectively (p < 0.05). In patients with an echo score of > 8, the influence of commissural calcification was smaller and not significant. CONCLUSIONS: Commissural calcification as assessed by transthoracic echocardiography is a useful predictor of outcome in patients with otherwise "good" valves (echo score </= 8). Calcification of one commissure or more predicts a less than 50% probability of achieving a valve area above 1.50 cm(2) and is an indication for valve replacement in those who are suitable for surgery.

Adolescent↗

Mitral annular calcification: a marker of severe coronary artery disease in patients under 65 years old.

BACKGROUND: Mitral annular calcification has been associated with various systemic and cardiac diseases, with a higher prevalence in women and patients over 70. A possible association between mitral annular calcification and coronary artery disease has recently been suggested. OBJECTIVE: To determine the prevalence of severe coronary artery disease in younger patients with mitral annular calcification. METHODS: Consecutive patients aged or= 70% stenosis of at least one major epicardial coronary artery. PATIENTS: 17 735 patients were screened. Of these, 6207 (35%) had mitral annular calcification and 885 (5%) were also <or= 65 years old; coronary angiography was done in 100 of the latter (64 men; 36 women), mainly for anginal symptoms or a positive stress test. A control group (n = 121; 88 men, 33 women) was identified from 2840 consecutive patients screened. There was no significant difference between the groups in patient characteristics, indication for angiography, or atherosclerotic risk factors. RESULTS: Angiography showed a higher prevalence of severe coronary artery disease in patients with mitral annular calcification than in those without (88% v 68%, p = 0.0004), and a higher prevalence of left main coronary artery disease (14% v 4%, p = 0.009) and triple vessel disease (54% v 33%, p = 0.002). The positive predictive value of mitral annular calcification for finding severe coronary artery disease was 92%. CONCLUSIONS: In patients aged <or= 65 years, mitral annular calcification is associated with an increased prevalence of severe obstructive coronary artery disease. It may serve as a useful echocardiographic marker for the presence of obstructive coronary artery disease, especially when associated with anginal symptoms.

Adult↗

Asymptomatic cerebral calcification--a previously unrecognized feature.

While investigating the radiological appearances of globus pallidus calcification in an autopsy case, cortical-pia mater calcification was detected. There was no documentation of its existence in the literature of radiology, neurology and neuropathology. To establish its incidence and clinical significance, 20 consecutive autopsy brains (15 males, 5 females, age 32-73 years, mean age 56.7) were studied with high resolution radiography and histology. Clinical records, autopsy findings, in-life plain skull films and computed tomography of the brain (if available) were reviewed. Radiologically, the calcifications appeared as 1-2 mm irregular spots or tiny pin-point opacities in the pia mater and subcortical regions, either unilaterally or bilaterally in the frontal (15 cases), temporal (15), parietal (3) and occipital lobes (1). Similar calcification was detected in 1 of the 3 in-life computed tomographic scans available. Histologically, these cortical-pia mater calcifications were extracellular amorphous calcified masses of various sizes in necrotic neural tissue, frequently associated with microscopic haemorrhage and hypoxic neuronal changes in the adjacent brain tissue. Blood vessels in the region were not hyalinized or calcified. The occurrence was not related to age. Hospital stay was less than 7 days in 14 and less than 30 days in 2; 50% of patients died within 48 hours after admission. None of the patients had records of long term cytotoxic chemotherapy, radiotherapy or central nervous system infection. Two had stroke, one had cerebellar atrophy and one mild hypercalcaemia. The high incidence of calcifications in the temporal lobes, while asymptomatic, suggests that cortical calcification may be a pointer to the aetiology of idiopathic epilepsies in the elderly.

Adult↗

Intrathoracic calcifications: radiographic features and differential diagnoses.

Intrathoracic calcifications occur in a wide variety of disorders. Although they are usually harmless sequelae of remote processes, calcifications provide important information for establishing the diagnosis or for evaluating the progression of known disease. They may arise in the pulmonary parenchyma, mediastinum, hilar and mediastinal lymph nodes, pleura, chest wall, or any combination of these structures. The cause of the calcification may be determined by means of the location and pattern of the calcifications within the lung parenchyma and knowledge of the associated clinical features. Calcifications in the thorax are frequently manifestations of previous infectious processes. Less often, they may be due to neoplasms, metabolic disorders, occupational exposure, or previous medical therapy. Large intrathoracid calcifications are usually identified on conventional chest radiographs; detection of smaller calcifications may require use of other imaging modalities, such as dual-energy digital radiography, fluoroscopy, radionuclide scanning, computed tomography (CT), and high-resolution CT.

Calcinosis↗

The diagnostic and prognostic significance of coronary artery calcification. A report of 800 cases.

The significance of coronary artery calcification was assessed in 800 patients who underwent cardiac fluoroscopy and selective coronary cineangiography. Calcification was shown by fluoroscopy in 250, of whom 236 (94%) had greater than or equal to 75% stenosis of one or more major coronary arteries at angiography. Among patients with significant coronary artery disease, 40% (236/585) had calcification. Patients with calcification demonstrated poorer survival at all follow-up intervals (from six months to five years); the five-year survival rate was 87% for patients without calcification, compared to 58% for those with calcification. The prognostic significance of coronary artery calcification appears to be independent of information obtained by cardiac catheterization and angiocardiography.

Calcinosis↗

Metastatic pulmonary calcifications after cardiac surgery in children.

Six children in whom pulmonary calcifications developed after open heart surgery are described. Asymptomatic alveolar lesions appeared within the first 3 weeks after surgery, during or after intensive care. They were first diagnosed as possible infection or edema and secondarily identified as calcifications in the lungs. In five patients, the pulmonary calcifications partially decreased or disappeared, and the prognosis did not seem to be altered. In one patient, the pulmonary calcifications were associated with cardiac calcifications leading to death. The mechanism of these pulmonary calcifications is thought to be predominantly or exclusively metastatic and partially iatrogenic. Data indicated two major causative factors: therapy with massive doses of calcium and postsurgical acute renal failure. Radiographic findings of persistent alveolar lesions of increasing density in patients undergoing antibiotic therapy after open heart surgery are suggestive of the diagnosis of metastatic pulmonary calcifications. Scintigraphy with bone agents or computed tomography is recommended for early confirmation and prevention of therapeutic errors, especially after cardiac transplantation.

Acute Kidney Injury↗

Focal calcifications in otherwise ultrasonographically normal ovaries.

PURPOSE: To analyze the natural history, clinical importance, and need for follow-up in patients with discrete calcifications in otherwise ultrasonographically (US) normal ovaries. MATERIALS AND METHODS: US scans obtained in 28 women with ovarian calcifications but without masses or other structural abnormalities were retrospectively reviewed. Follow-up findings were available in 15 women (mean age, 38.0 years; range, 26-72 years). RESULTS: Two of the 15 women had trilateral calcifications. Thus, 17 ovaries had focal calcifications. Histopathologic confirmation was obtained in 10 cases; follow-up US findings, five cases; and follow-up laparoscopic findings, two cases. In 13 (76%) of the 17 ovaries, calcifications were not clinically important. In four (24%) of the 17, the calcification was the initial or only manifestation of a neoplasm. Lesions were benign in all four of these ovaries: There was one dermoid, one mucinous cystadenoma, and two adenofibromas. CONCLUSION: Until more data are available, findings of calcifications in ovaries with otherwise normal US findings warrant some form of follow-up.

Adult↗

Aortic calcification produced by vitamin D3 plus nicotine.

Calcification of the elastic arteries of the young rat by treatment with vitamin D and nicotine (VDN) has been proposed as an animal model of arterial calcification associated with age and age-related vascular pathology in man. The calcium-binding protein, S-100, which is found in human atherosclerotic lesions was associated with medial calcification of the aorta in VDN rats, especially in cases of severe calcification. Calcification (total calcium content: 366 +/- 87, n = 12 in VDN vs. 24 +/- 2 micromol g(-1) aortic dry weight in controls, n = 13) involved elastocalcinosis leading to elastolysis as revealed by a fall in the amount of desmosine and isodesmosine in the aortic wall (266 +/- 17 and 254 +/- 15 in VDN vs. 655 +/- 56 and 588 +/- 30 microg g(-1) aortic dry weight in controls). The decrease in elastin was associated with an increase in the stiffness of the aortic wall (elastic modulus: 15.1 +/- 1.8 in VDN vs. 6.7 +/- 0.5 10(6) dyn cm(-2) in controls), an increase in end-systolic stress (central systolic aortic pressure: 152 +/- 6 in VDN vs. 136 +/- 2 mm Hg in controls) (at a normotensive mean pressure level) and left ventricular hypertrophy (heart weight/body weight 2.51 +/- 0.10 in VDN vs. 2.24 +/- 0.07 g kg(-1) in controls). In conclusion, the mechanisms and consequences of aortic calcification in VDN show several similarities with calcification occurring in human athero- and arteriosclerosis.

Anesthesia↗

Aortic calcifications and their relationship to coronary heart disease and cardiovascular risk factors in patients with newly diagnosed non-insulin-dependent diabetes and in nondiabetic subjects.

The prevalence of radiologically detectable aortic calcifications, the cross-sectional area of the aortic arch, pulse wave velocity and cardiovascular risk factors were examined in 133 newly diagnosed non-insulin-dependent diabetic patients aged 45-64 years and in 144 randomly selected control subjects of the same age. In addition, the relationship between aortic calcifications and coronary heart disease was examined. Diabetic men tended to have more frequently calcifications in the abdominal aorta than nondiabetic men, whereas such a difference was not found between diabetic and nondiabetic women. No difference was observed between diabetic and nondiabetic subjects in the prevalence of calcifications of the aortic arch. Among cardiovascular risk factors, smoking was associated with calcifications of the abdominal aorta in diabetic and nondiabetic men. Ischemic ECG abnormalities at rest showed a statistically significant association with the presence of abdominal aortic calcifications in diabetic men. The cross-sectional area of the aortic arch increased with age in both in diabetic and in nondiabetic subjects and was larger in diabetic than in nondiabetic men. Diabetes did not show any significant effect on pulse wave velocity. An increased frequency of calcifications of the abdominal aorta and a dilatation of the aortic arch in newly diagnosed non-insulin-dependent men as compared with nondiabetic men is compatible with the view that an accelerated development of atherosclerotic lesions of large arteries starts already in an early, asymptomatic phase of this type of diabetes.

Aorta, Abdominal↗

Mineralization of collagen and elastic fibers in superficial dystrophic cutaneous calcification: an ultrastructural study.

The ultrastructural morphology of localized skin calcifications without associated diseases and with normal serum calcium and phosphate ion values is still unknown. In a case of superficial dystrophic calcinosis cutis (DCC), the role of collagen, elastin and ground substance in the process of calcification and the organization of the apatite crystals could be studied by light and electron microscopy despite technical difficulties in sectioning the hard tissue. Ultrastructural investigation revealed the nucleation of calcification being related to collagen and elastic fibers. No intracellular calcification was found. A flower-like arrangement of pleomorphic crystals was found around single collagen fibrils resembling the calcification of collagen seen in bone tissue. The elastic fibers showed a different pattern of calcification compared with other diseases (e.g. pseudoxanthoma elasticum) with known calcification of the elastic fibers. The process of mineralization was initially linked to the microfibrils of the elastic fiber.

Adult↗

Decorin promotes aortic smooth muscle cell calcification and colocalizes to calcified regions in human atherosclerotic lesions.

OBJECTIVE: Ectopic calcification localized to the intima of atherosclerotic plaque is a risk marker for cardiovascular events and increases the risk of aortic dissection during angioplasty. A variety of extracellular matrix molecules such as collagen type 1, bone sialoprotein, and osteopontin are known to regulate the biomineralization of bone and ectopic vascular calcification. In the present study, it was investigated whether decorin, a small leucine-rich proteoglycan expressed in bone and atherosclerotic plaque, is involved in arterial calcification. METHODS AND RESULTS: Calcification was induced in cultured bovine aortic smooth muscle cell (BASMC) by the addition of beta-glycerophosphate or inorganic phosphate. Northern and Western analysis revealed that decorin expression was strongly upregulated in mineralizing BASMC. Furthermore, overexpression of decorin using a retroviral expression vector resulted in a 3- to 4-fold elevation of calcium deposited on the BASMC monolayer. Increased calcification in response to decorin could also be mimicked by adding exogenous decorin to the cultures. In addition, human coronary atherosclerotic lesions taken from sudden-death patients showed marked colocalization of calcium deposits with decorin. CONCLUSIONS: Decorin induces calcification of arterial smooth muscle cell cultures and colocalizes to mineral deposition in human atherosclerotic plaque, suggesting that decorin functions as promoter of intimal calcification.

Animals↗

Matrix metalloproteinase inhibition attenuates aortic calcification.

OBJECTIVE: Arterial calcification has been associated with matrix metalloproteinase (MMP)-mediated elastin degradation. In this study, we investigated whether inhibiting MMP activity could reduce calcium accumulation in rodent models of aortic calcification. METHODS AND RESULTS: Aortic calcification was first induced in male Sprague-Dawley rats by administration of vitamin D3. Treatment with doxycycline decreased aortic calcium and phosphorus accumulation, and it reduced aortic gelatinase levels; however, it also prevented the bone resorption associated with high doses of vitamin D3. Using an in vivo model of localized aortic calcification, systemic doxycycline treatment reduced aortic calcium accumulation without affecting serum calcium levels, suggesting a more specific effect of doxycycline in the arterial wall. In organ culture, doxycycline limited aortic calcification caused by exposure to alkaline phosphatase and inorganic phosphate. When GM6001, a synthetic and specific inhibitor of MMPs, was used instead of doxycycline, it had a similar effect. In vivo, periadventitial delivery of GM6001 to calcifying arteries significantly reduced calcification compared with controls. CONCLUSIONS: These results suggest that MMPs are involved in aortic calcification, and inhibiting MMP activity could reduce calcium accumulation in the arterial wall.

Animals↗

Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves.

High doses of warfarin cause focal calcification of the elastic lamellae in the media of major arteries and in aortic heart valves in the rat. Aortic calcification was first seen after 2 weeks of warfarin treatment and progressively increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the highly focal calcification of major arteries could be seen on radiographs and by visual inspection of the artery. The calcification of arteries induced by warfarin is similar to that seen in the matrix Gla protein (MGP)-deficient mouse, which suggests that warfarin induces artery calcification by inhibiting gamma-carboxylation of MGP and thereby inactivating the putative calcification-inhibitory activity of the protein. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum. Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal. The results indicate that the improved warfarin plus vitamin K treatment protocol developed in this study should provide a useful model to investigate the role of MGP in preventing calcification of arteries and heart valves.

Animals↗

Coronary and aortic calcification among women 8 years after menopause and their premenopausal risk factors : the healthy women study.

In the Healthy Women Study, the relationship between cardiovascular risk factors measured premenopausally at age 48, use of hormone therapy, and coronary and aortic calcification at age 58 were evaluated among 169 women. Approximately 63% of women had no coronary calcification, but only 29% had no aortic calcification. Coronary calcification and aortic calcification were positively correlated with each other. There was a very strong association between low density lipoprotein cholesterol (LDL-C) level and coronary calcification. Among women with premenopausal levels of LDL-C <100 mg/dL, only 9% had a coronary calcium score >/=101 compared with 30% of women with an LDL-C >160 mg/dL. Only 5% of women with a high density lipoprotein cholesterol (HDL-C) level >60 mg/dL had high coronary scores. The level of HDL(2)-C was especially strongly inversely related to coronary calcium scores. Cigarette smoking was a very important determinant of both high aortic and high coronary calcium scores. Other risk factors associated with greater coronary calcium were higher systolic blood pressure, triglycerides levels, and blood glucose. Use of hormone replacement therapy was associated with less coronary calcium (NS). For both hormone replacement therapy users and nonusers, the levels of LDL-C and HDL-C measured premenopausally were predictors of coronary and aortic calcium scores. Thus, risk factors evaluated premenopausally are powerful predictors of coronary and aortic calcification, a marker of atherosclerosis, measured 8 years after menopause, 11 years later in these women.

Aortic Diseases↗

The impact of calcification on the biomechanical stability of atherosclerotic plaques.

BACKGROUND: Increased biomechanical stresses in the fibrous cap of atherosclerotic plaques contribute to plaque rupture and, consequently, to thrombosis and myocardial infarction. Thin fibrous caps and large lipid pools are important determinants of increased plaque stresses. Although coronary calcification is associated with worse cardiovascular prognosis, the relationship between atheroma calcification and stresses is incompletely described. METHODS AND RESULTS: To test the hypothesis that calcification impacts biomechanical stresses in human atherosclerotic lesions, we studied 20 human coronary lesions with techniques that have previously been shown to predict plaque rupture locations accurately. Ten ruptured and 10 stable lesions derived from post mortem coronary arteries were studied using large-strain finite element analysis. Maximum stress was not correlated with percentage of calcification, but it was positively correlated with the percentage of lipid (P:=0.024). When calcification was eliminated and replaced with fibrous plaque, stress changed insignificantly; the median increase in stress for all specimens was 0.1% (range, 0% to 8%; P:=0.85). In contrast, stress decreased by a median of 26% (range, 1% to 78%; P:=0.02) when lipid was replaced with fibrous plaque. CONCLUSIONS: Calcification does not increase fibrous cap stress in typical ruptured or stable human coronary atherosclerotic lesions. In contrast to lipid pools, which dramatically increase stresses, calcification does not seem to decrease the mechanical stability of the coronary atheroma.

Adult↗

Balloon dilatation of calcific aortic stenosis in elderly patients: postmortem, intraoperative, and percutaneous valvuloplasty studies.

To assess the safety and efficacy of percutaneous balloon valvuloplasty in calcific aortic stenosis, balloon dilatation of critically stenosed, calcified aortic valves was performed in five postmortem hearts, in five patients intraoperatively before aortic valve replacement, and in two elderly patients percutaneously at the time of diagnostic catheterization. The etiology of aortic stenosis in the 12 cases was rheumatic in two, congenital bicuspid calcific stenosis in one, and senile calcific degenerative stenosis in the remaining nine. Prevalvuloplasty examination in the 10 postmortem and intraoperative cases revealed rigid valve leaflets with commissural fusion in three valves and extensive nodular calcification in seven. Subsequent balloon dilatation with 15 to 18 mm valvuloplasty balloons resulted in decreased cusp rigidity and increased mobility of valve leaflets in all cases, without evidence of tearing of valve leaflets, disruption of the valvular ring, or liberation of calcific or valvular debris. In the three valve specimens with commissural fusion, balloon dilatation resulted in partial or complete separation of leaflets along fused commissures. In two cases with extensive nodular calcification, balloon dilatation resulted in a fracture of a calcified leaflet that was evident on both gross and radiologic examination. After postmortem and intraoperative studies, percutaneous catheter valvuloplasty was performed at the time of diagnostic catheterization in two elderly patients (93- and 85-year-old women) with long-standing calcific aortic stenosis. Balloon dilatation with 12 to 18 mm balloons resulted in significant decreases in aortic gradients and significant increases in cardiac index and aortic valve area in both patients. Percutaneous valvuloplasty in both patients resulted in a mild increase in aortic insufficiency and no evidence of embolic phenomena.

Aged↗

Chemically determined mineral content of explanted porcine aortic valve bioprostheses: correlation with radiographic assessment of calcification and clinical data.

Bioprosthetic valve calcification is usually assessed pathologically by gross inspection, radiographic studies, and histologic examination. Quantitation of mineral content by chemical assay has not been reported for failed clinical valves removed from adults. In this study, calcium determination by atomic absorption spectroscopy was done on 52 removed porcine valves after routine pathologic examination, including specimen radiography done by a standard technique. Specimens included 31 valves with calcific primary tissue failure, two calcified (but not overtly dysfunctional) valves removed simultaneously with failed valves, 14 nondeteriorated valves obtained at reoperation or autopsy after long-term implantation, and five valves removed within 1 month after insertion. Chemically determined mineral content varied widely among patients and duration of function. Valves with calcific failure had 113 +/- 68 micrograms/mg calcium overall (mean +/- SD) after 36 to 156 months (mean 87) of function. Almost all dysfunctional porcine valves with radiographically demonstrated calcific deposits had greater than 34 and 67 micrograms/mg calcium for mitral and aortic valves, respectively. Nondeteriorated valves (implanted 8 to 145 months, mean 57) had 5 +/- 6 micrograms/mg calcium. Failed aortic valves had more calcium than failed mitral valves and valves with calcific stenosis more than valves with regurgitation caused by calcification with tearing. Correlation of semiquantitative radiographic grading with chemically determined valve mineral was good, indicating that radiographic assessment of calcification may be used reliably for clinical comparisons between valves.

Aortic Valve↗

Coronary calcification and its relation to extracoronary atherosclerosis in asymptomatic hypercholesterolemic men. The PCV METRA Group.

BACKGROUND: The prevalence of coronary calcifications and extracoronary plaques was studied in patients with asymptomatic hypercholesterolemia. METHODS AND RESULTS: Ultrafast computed tomography for coronary calcification (presence or absence: calcium score) and echographic assessment of carotid, aortic, and femoral plaques were performed in 111 hypercholesterolemic men: 65% had coronary calcification, 72% had extracoronary plaque. The two lesions were associated as: 1) compared with subjects without coronary calcification, those with calcification had a higher prevalence of aortic (p less than 0.05) and femoral (p less than 0.01) plaque and of two diseased sites (p less than 0.05); 2) the prevalence of coronary calcification was higher in the presence than in the absence of aortic (p less than 0.05) or femoral (p less than 0.01) plaque and higher in two (p less than 0.01) and three diseased (p less than 0.05) sites than in no diseased site; 3) the calcium score was higher in the presence than in the absence of carotid (p less than 0.05), aortic (p less than 0.05), or femoral (p less than 0.001) plaque, higher in two (p less than 0.001) and three diseased (p less than 0.05) sites than in no diseased sites, and higher in two (p less than 0.01) than in one diseased site; and 4) the calcium score correlated with femoral plaque (p less than 0.001). Overall, the presence of two or three diseased extracoronary sites versus no or one diseased site showed a power of 78% for predicting coronary calcification. Coronary calcium score correlated with age (p less than 0.01) and triglycerides (p less than 0.05). CONCLUSIONS: The close relation between coronary calcium and extracoronary plaques suggests that echography of extracoronary vessels could aid in the screening of coronary atherosclerosis in high-risk, asymptomatic individuals.

Adult↗