cardiovascular-agents and Calcinosis

This review summarizes current understanding of generalized arterial calcification of infancy (GACI), emphasizing pathophysiology, clinical presentation, and approaches and controversies in management.. Identification of causative ENPP1 mutations revealed that GACI arises from deficiencies in inorganic pyrophosphate (leading to calcifications) and adenosine monophosphate (leading to intimal proliferation). Identification of genotypic and phenotypic overlap with pseudoxanthoma elasticum and autosomal recessive hypophosphatemic rickets further advanced understanding of GACI as a complex, multisystemic disease. Clinical data is limited to small, retrospective samples; it is therefore unknown whether commonly used medications, such as bisphosphonates and hypophosphatemia treatment, are therapeutic or potentially harmful. ENPP1-Fc replacement represents a promising approach warranting further study. Knowledge gaps in natural history place clinicians at high risk of assigning causality to interventions that are correlated with changes in clinical status. There is thus a critical need for improved natural history studies to develop and test targeted therapies.

Topics: Adenosine Monophosphate; Bone Density Conservation Agents; Calcinosis; Cardiovascular Agents; Chelating Agents; Diphosphates; Diphosphonates; Familial Hypophosphatemic Rickets; Genotype; Hearing Loss; Humans; Multidrug Resistance-Associated Proteins; Phenotype; Phosphoric Diester Hydrolases; Pseudoxanthoma Elasticum; Pyrophosphatases; Thiosulfates; Tooth Diseases; Vascular Calcification; Vitamin D

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). Genetic, epidemiological and in vitro data provide strong evidence for a pathogenic role for Lp(a) in the progression of atherothrombotic disease. Despite these advancements and a race to develop new Lp(a) lowering therapies, there are still many unanswered and emerging questions about the metabolism and pathophysiology of Lp(a). New studies have drawn attention to Lp(a) as a contributor to novel pathogenic processes, yet the mechanisms underlying the contribution of Lp(a) to CVD remain enigmatic. New therapeutics show promise in lowering plasma Lp(a) levels, although the complete mechanisms of Lp(a) lowering are not fully understood. Specific agents targeted to apolipoprotein(a) (apo(a)), namely antisense oligonucleotide therapy, demonstrate potential to decrease Lp(a) to levels below the 30-50 mg/dL (75-150 nmol/L) CVD risk threshold. This therapeutic approach should aid in assessing the benefit of lowering Lp(a) in a clinical setting.

Topics: Aortic Valve; Aortic Valve Stenosis; Calcinosis; Cardiovascular Agents; Coronary Disease; Humans; Lipoprotein(a); Oligonucleotides, Antisense; Risk Factors; Translational Research, Biomedical

A metamorphosis in the etiology of valvular heart disease (VHD) has occurred over the last 6 decades. In this review, the factors contributing to this metamorphosis, the common causes of VHD today, the relationship of valvular calcification to atherosclerosis and the interrelationship of VHD with other systems/organs are presented.

Topics: Calcinosis; Cardiomyopathies; Cardiovascular Agents; Disease Susceptibility; Endocarditis; Female; Heart Neoplasms; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Iatrogenic Disease; Male; Pedigree; Renal Insufficiency, Chronic

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcinosis; Cardiovascular Agents; Diabetic Angiopathies; Fibrosis; Heart Failure; Humans; Hypoglycemic Agents; Myocardium; Prognosis; Risk Factors

Topics: Aortic Valve Insufficiency; Aortic Valve Stenosis; Calcinosis; Cardiovascular Agents; Heart Valve Diseases; Humans; Mitral Valve Insufficiency; Mitral Valve Stenosis; Risk Factors

Topics: Antihypertensive Agents; Arterioles; Arteriosclerosis; Basement Membrane; Bone Remodeling; Calcinosis; Calcium; Cardiovascular Agents; Cardiovascular Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Diagnostic Tests, Routine; Disease Progression; Humans; Hyperparathyroidism; Hypertension; Hypertrophy, Left Ventricular; Kidney Transplantation; Osteoblasts; Renal Dialysis; Uremia; Vascular Diseases; Venules; Vitamin D

To compare the intravascular ultrasound virtual histology (IVUS-VH) appearance of the polymeric struts of the first (Revision 1.0) and the second (Revision 1.1) generation bioresorbable vascular scaffold (BVS).. IVUS-VH misrepresents polymeric struts as dense calcium (DC) and necrotic core (NC) so that their presence and disappearance could be used as potential artifactual surrogate of bioresorption. DC and NC were assessed in both revisions of the BVS by analysing IVUS-VH from all patients in the ABSORB cohort A (Revision 1.0) and cohort B (Revision 1.1) study who had an IVUS-VH post-treatment and at 6-month follow-up. Post-treatment and 6-month follow-up IVUS-VH results, available in 60 patients (BVS 1.0 n=28; BVS 1.1 n=32), indicated an insignificant rise in DC+NC area compared to baseline with Revision 1.1 (0.10 ± 0.46 mm2, p=0.2), whilst a significant reduction was seen with Revision 1.0 (-0.57 ± 1.3 mm2, p=0.02). A significant correlation has been found between the change in the DC+NC area and the change in external elastic membrane area (y=0.68x-0.1; r=0.58, p=0.03).. Based on 6-months IVUS-VH analysis, the BVS 1.1 appears to have a different backscattering signal compared to the BVS 1.0, which may reflect differences in the speed of chemical and structural alteration.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Australia; Calcinosis; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Necrosis; New Zealand; Polyesters; Prosthesis Design; Sirolimus; Time Factors; Tissue Scaffolds; Treatment Outcome; Ultrasonography, Interventional

Little is known about the impact of treatment with drug-eluting stents (DES) on calcified coronary lesions. This analysis sought to assess the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) in patients with calcified or noncalcified culprit lesions.. The study population consisted of 212 patients with 247 lesions, who were treated with EES alone. Target lesions were angiographically classified as none/mild, moderate, or severe grades of calcification. The population was divided into two groups: those with at least one target lesion moderately or severely calcified (the calcified group: 68 patients with 75 calcified lesions) and those with all target lesions having mild or no calcification (the noncalcified group: 144 patients). Six-month and 2-year angiographic follow-up and clinical follow-up up to 3 years were completed.. The baseline characteristics were not significantly different between both groups. When compared with the noncalcified group, the calcified group had significantly higher rates of 6-month in-stent angiographic binary restenosis (ABR, 4.3% vs. 0%, P = 0.03) and ischemia-driven target lesion revascularization (ID-TLR, 5.9% vs. 0%, P = 0.01), resulting in numerically higher major cardiac adverse events (MACE, 5.9% vs. 1.4%, P = 0.09). At 2 years, when compared with the noncalcified group, the calcified group presented higher in-stent ABR (7.4% vs. 0%, P = 0.08) and ID-TLR (7.8% vs. 1.5%, P = 0.03), resulting in numerically higher MACE (10.9% vs. 4.4%, P = 0.12). At 3 years, ID-TLR tended to be higher in the calcified group than in the noncalcified group (8.6% vs. 2.4%, P = 0.11), resulting in numerically higher MACE (12.1% vs. 4.7%, P = 0.12).. The MACE rates in patients treated with EES for calcified lesions were higher than in those for noncalcified lesions, but remained lower than the results of previously reported stent studies. EES implantation in patients with calcified culprit lesions was safe and associated with favorable reduction of restenosis and repeat revascularization. © 2010 Wiley-Liss, Inc.

Topics: Aged; Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; India; Kaplan-Meier Estimate; Male; Middle Aged; New Zealand; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

The main objective was to use IVUS-backscatter radiofrequency (IVUS-RF) to assess the degradation of a bioabsorbable stent by measuring serial changes in dense calcium (DC) and necrotic core (NC) as assessed by intravascular ultrasound-Virtual Histology (IVUS-VH) and in the strain as assessed by palpography.. In the ABSORB trial, 27 patients treated with a single bioabsorbable everolimus-eluting stent (BVS, Abbott Vascular, Santa Clara, CA, USA) were all imaged with IVUS-RF post-stenting and at 6-month follow-up, and 13 and 12 patients were also investigated pre-stenting with IVUS-VH and palpography respectively. From pre- to post-stenting, with VH (n = 13), there was an increase in mean "DC" (9.8 vs. 25.4%, p = 0.0002) and "NC" (15.5 vs. 30.5%, p = 0.0002). In palpography (n = 12), the mean number of frames with Rotterdam Classification (ROC) III/IV per cm decreased from 1.22 +/- 1.91 to 0.12 +/- 0.31 (p = 0.0781) and the mean cumulative strain values (all frames with ROC I-IV scores) changed from 0.50 +/- 0.27 to 0.20 +/- 0.10% (p = 0.0034). Comparing post-stenting with follow-up (n = 27), VH showed a decrease in "DC" (29.7% vs. 21.1%, p = 0.0001). "NC" also decreased (26.9 vs. 21.5%, p = 0.0027). For palpography (n = 25 patients), an increase in the mean number of frames with ROC III/IV per cm was observed from 0.09 +/- 0.26 to 0.22 +/- 0.36 (p = -0.1563) while the mean cumulative strain values (all frames with ROC I-IV scores) changed from 0.15 +/- 0.10 to 0.26 +/- 0.12% (p < 0.0001).. IVUS-VH changes at 6 months suggest alteration of the BVS with reduction of RF backscattering by polymeric struts. Strained plaques on the palpograms were almost abolished following stent implantation. However, strain values reappeared within 6 months suggesting an increase in endoluminal deformability of the stented vessel.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; Coronary Artery Disease; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Necrosis; New Zealand; Prospective Studies; Prosthesis Design; Sirolimus; Stress, Mechanical; Time Factors; Treatment Outcome; Ultrasonography, Interventional; User-Computer Interface

Topics: Aortic Valve; Aortic Valve Stenosis; Calcinosis; Cardiovascular Agents; Endothelial Cells; ERRalpha Estrogen-Related Receptor; Gene Regulatory Networks; Humans; Induced Pluripotent Stem Cells; Machine Learning; Nitriles; Receptor, Notch1; Receptors, Estrogen; Thiazoles

The development of a substance or inhibitor-based treatment strategy for the prevention of aortic valve stenosis is a challenge and a main focus of medical research in this area. One strategy may be to use the tankyrase inhibitor XAV-939, which leads to Axin stabilisation and subsequent destruction of the β-catenin complex and dephosphorylation of β-catenin. The dephosphorylated active form of β-catenin (non-phospho-β-catenin) then promotes nuclear transcription that leads to osteogenesis. The aims of the present study were to develop an experimental system for inducing in vitro calcification of human aortic valvular interstitial cells (VICs) to investigate the potential anti-calcific effect of XAV-939 and to analyse expression of the Wnt signalling proteins and Sox9, a chondrogenesis regulator, in this model. Calcification of human VIC cultures was induced by cultivation in an osteogenic medium and the effect of co-incubation with 1μM XAV-939 was monitored. Calcification was quantified when mineral deposits were visible in culture and was histologically verified by von Kossa or Alizarin red staining and by IR-spectroscopy. Protein expression of alkaline phosphatase, Axin, β-catenin and Sox9 were quantified by western blotting. In 58% of the VIC preparations, calcification was induced in an osteogenic culture medium and was accompanied by upregulation of alkaline phosphatase. The calcification induction was prevented by the XAV-939 co-treatment and the alkaline phosphatase upregulation was suppressed. As expected, Axin was upregulated, but the levels of active non-phospho-β-catenin were also enhanced. Sox9 was induced during XAV-939 treatment but apparently not as a result of downregulation of β-catenin signalling. XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process.

Topics: Aged; Alkaline Phosphatase; Aortic Valve; Aortic Valve Stenosis; beta Catenin; Calcinosis; Cardiovascular Agents; Cells, Cultured; Female; Heterocyclic Compounds, 3-Ring; Humans; Male; Protective Agents; SOX9 Transcription Factor; Wnt Proteins

Topics: Calcinosis; Calcium; Cardiovascular Agents; Coronary Artery Disease; Drug Therapy, Combination; Humans; Polypharmacy

Topics: Calcinosis; Calcium; Cardiovascular Agents; Coronary Artery Disease; Humans; Polypharmacy

Topics: Calcinosis; Calcium; Cardiovascular Agents; Coronary Artery Disease; Humans; Polypharmacy

Topics: Acute Coronary Syndrome; Aged, 80 and over; Aortic Diseases; Atherosclerosis; Calcinosis; Cardiovascular Agents; Colitis, Ischemic; Dietary Supplements; Humans; Hyperparathyroidism, Secondary; Hypertension; Hypotension; Kidney Failure, Chronic; Male; Myocardial Ischemia; Nephrosclerosis; Obesity; Parenteral Nutrition; Pneumatosis Cystoides Intestinalis; Renal Dialysis; Splanchnic Circulation

The case is reported of a 28-year-old subject with a bioprosthesis (Shelhigh 31) in the aortic position, with symptoms of heart failure and possible prosthetic dysfunction. As the echocardiographic interrogation remained inconclusive, the patient underwent cardiovascular magnetic resonance (CMR) imaging, which revealed an impaired movement of the non-coronary cusp. In addition, computed tomography (CT) demonstrated severe calcification of the immobile prosthetic component. Hence, in selected patients, both CMR and CT can be used as complementary tools to evaluate the dysfunction and pathology of heart valve bioprostheses.

Topics: Adult; Aortic Valve; Bioprosthesis; Calcinosis; Cardiovascular Agents; Drug Therapy, Combination; Heart Failure; Heart Function Tests; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Magnetic Resonance Imaging; Male; Postoperative Complications; Prosthesis Failure; Stroke Volume; Tomography, X-Ray Computed; Treatment Outcome; Ventricular Remodeling

Topics: Aged; Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Calcinosis; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Microscopy, Electron, Scanning; Polymers; Prosthesis Design; Prosthesis Failure; Sirolimus; Surface Properties; Treatment Outcome

Chronic constrictive pericarditis (CCP) is a clinical syndrome caused by compression of the heart due to a thickened or rigid pericardium. In the affluent West, the majority of cases of CCP are neither tuberculous nor calcific. In an American cohort undergoing pericardectomy for the condition, only 27% had calcification and under 10% had TB [1]. As a result, pericardial calcification (PC) as a marker of CCP has become neglected. We present a 48-year-old male admitted with atrial flutter, acute chest infection and signs of right heart congestion. PC was documented one year previously on a non-contrast CT chest. On this occasion, cardiac catheterisation confirmed hemodynamically significant CCP and cardiac magnetic resonance (cMR) study showed contiguous mass lesions in the pericardium, compression of the right ventricle, enlargement of the right atrium, hepatic enlargement and a pneumonic process in the left lung. He was commenced on antibiotics and anti-tuberculous therapy with a diagnosis of bacterial super-infection of tuberculous CCP. This was confirmed at pericardectomy along with an infected fistula into the left lung. Any finding of PC should be followed up with a thorough haemodynamic and anatomical assessment using any of a wide range of non-invasive imaging modalities.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Calcinosis; Cardiac Catheterization; Cardiovascular Agents; Chronic Disease; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pericardiectomy; Pericarditis, Constrictive; Pericarditis, Tuberculous; Superinfection; Tomography, X-Ray Computed; Treatment Outcome

Calcified coronary lesions have commonly been considered as a challenge for interventional cardiologists, and few previous studies of sirolimus-eluting stent (SES) for calcified lesion have been limited by small sample size. Therefore, we evaluated the effectiveness of SES implantation for the treatment of calcified lesions in a large Chinese cohort of real world practice.. A total of 956 consecutive patients who successfully received SES placement were enrolled in this study, and were divided into the two groups according to whether the mild-moderate calcified lesion treated with SES exists or not: noncalcified group (n = 637) and calcified group (n = 319). Lesions treated with SES were subjected to quantitative coronary angiography immediately and 8 months after stenting.. Baseline characteristics including clinical, demographic or angiographic data were well balanced between the noncalcified and calcified groups. In the angiographic follow-up at 8 months, the in-stent restenosis and in-segment restenosis rates were similar in both the groups (in-stent restenosis: 3.8 vs. 4.0%, P>0.05; in-segment restenosis: 8.5 vs. 9.7%, P>0.05). The target lesion revascularization was not different between the two groups (5.2 vs. 6.8%; P>0.05). In addition, the in-stent late loss and overall thrombosis rate were also similar in both the groups (0.17+/-0.41 vs. 0.18+/-0.35 mm and 1.8 vs. 1.8%, P>0.05, respectively).. Although stenting of the calcified lesion was hard, successful treatment with SES for mild-moderate calcified lesions was conferred to similar favorable results compared with noncalcified lesions in patients with coronary artery disease.

Topics: Aged; Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; China; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Our aim was to access the incidence of late major adverse cardiac events (MACE) and stent thrombosis (ST) in nonselected, complex patients followed for a period >/=4 years.. Despite the efficacy of drug-eluting stents (DES) in reducing repeated target lesion revascularization, concerns regarding the occurrence of late and very late ST have partially obscured the benefits of this novel technology.. All consecutive patients treated solely with DES between May 2002 and January 2005 were enrolled into this prospective, nonrandomized, single-center registry. The primary end point was long-term occurrence of MACE up to 7 years. Independent predictors of MACE, cardiac death, target lesion revascularization, and ST were obtained by a multivariate Cox proportional hazards regression model.. A total of 1,010 patients were enrolled. Most of them were men (77%) with a mean age of 63.7 years. Stent/patient rate was 1.4. Patients were kept in dual antiplatelet therapy for 3 and 6 months after Cypher (Cordis, Johnson & Johnson, Miami Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) stent implantation, respectively. Follow-up was obtained in 98.2% of the cohort (median 5.01 years). Survival free of MACE and cumulative incidence of definite/probable ST were 84.6% and 1.7%, respectively. Independent predictors of ST were percutaneous coronary intervention in the setting of acute myocardial infarction, DES overlapping, treatment of multivessel disease, presence of moderate-to-severe calcification at lesion site, and in-stent residual stenosis.. The deployment of DES in complex, real-world patients resulted in a low rate of very long-term MACE and ST. However, ST still occurs very long after the index procedure.

Topics: Aged; Angioplasty, Balloon, Coronary; Brazil; Calcinosis; Cardiovascular Agents; Coronary Restenosis; Disease-Free Survival; Drug Therapy, Combination; Drug-Eluting Stents; Female; Heart Diseases; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Prosthesis Design; Risk Assessment; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Sirolimus-eluting stent (SES) has revolutionized interventional cardiology. Its application is spreading to complex, high-risk subsets of patients and lesions. Therefore, it is important to determine the factors associated with post-SES restenosis.. The study investigated 341 patients with angina pectoris, in whom SES was implanted. The coronary artery calcification (CAC) degree was assessed using the angiographic scoring system as follows: 0, none; 1, blocky or spotty calcification; 2, linear calcification compromising 1 side of the arterial lumen; 3, linear calcification found unidirectionally compromising both sides of the arterial lumen; 4, linear calcification found bidirectionally compromising both sides of the arterial lumen; and 5, blanket/circumferential and dense calcification. Restenosis was observed in 23 patients (7.3%). The target lesion (1.8 +/-1.7 vs 0.7 +/-1.1 [mean +/- SD]) and stent delivery route CAC scores (3.1 +/-2.5 vs 1.4 +/-2.0) were significantly higher in patients with restenosis than in those without it (P<0.0001). In multivariate analysis, the CAC score of the stent delivery route was independently associated with restenosis (odds ratio of 6.804, P<0.05), although CAC score of the target lesion was not.. CAC in the stent delivery route is an important determinant of post-SES restenosis.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Microscopy, Electron; Middle Aged; Odds Ratio; Prosthesis Failure; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Sirolimus; Treatment Outcome

Although previously reported studies on coronary calcification mainly focused on its presence or absence in discrete focal target lesions, calcified coronary lesions (CCL) angiographically present as diffuse long lesions in some patients. The aim of our study was to evaluate the long-term efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) on long CCL.. A total of 122 patients with 134 lesions (77 patients with 88 lesions for SES and 45 patients with 46 lesions for PES) were enrolled from 3 centers. Long CCL was defined visually as a culprit lesion with type B or C that was mainly due to coronary calcification with > 20 mm in total length by coronary angiography. Clinical follow-up was performed at 1 year and angiographic follow-up at 6 to 9 months after procedure. Major adverse coronary events (MACE) were defined as all-cause death, myocardial infarction (MI), and repeat target-lesion revascularization (TLR).. There were no statistically significant differences in baseline, procedural, or angiographic characteristics and in 1-year rates of all-cause death, MI, and TLR between the 2 groups (all P = NS [not significant]). Likewise, the cumulative incidence of MACE at 1 year was similar between the 2 groups (7.8% of patients in the SES group vs 4.4% of patients in the PES group, respectively, P = NS). In patients who underwent follow-up angiography, the angiographic binary restenosis rate was 6.2% in the SES group vs 12.1% in the PES group, respectively (P = NS).. In patients with long CCL, both SES and PES were comparably effective in either angiographic or clinical long-term outcomes.

Topics: Aged; Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Republic of Korea; Retrospective Studies; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Durability remains the main problem of all bioprosthetic valves, and calcification is the major cause of failure. New tissue treatment processes are expected to reduce mineralization. A comparative animal study was undertaken to evaluate the behavior of a new-generation porcine bioprosthesis in contrast with a first-generation porcine bioprosthesis. The primary goal was to evaluate the efficacy of alpha-amino-oleic acid as an anticalcification treatment.. Seventeen Targhee sheep (aged 4.5-7 months) had a mitral valve replacement with a Mosaic or Hancock Standard. The animals were followed up to 20 weeks (144.1 +/- 4.0 days vs 144.3 +/- 8.2 days) and then euthanized as scheduled. After gross examination, the explants were radiographed for the presence of calcification. The central portions were preserved for histologic examination, and the remainder of the sample was analyzed for quantitative calcium content by atomic absorption spectroscopy.. Four Mosaic sheep were excluded because of perioperative surgical mortality. The remaining 13 were enrolled in the study (9 Mosaic and 4 Hancock Standard). The mean calcium content was 1.97 +/- 2.21 microg/mg tissue weight for Mosaic versus 8.36 +/- 4.12 microg/mg for Hancock Standard valves (P < .01). Mild fibrous tissue overgrowth and fibrinous lining were observed regardless the xenograft type.. The low level of calcification in the Mosaic versus Hancock Standard xenografts confirms the efficacy of alpha-amino-oleic acid treatment in mitigating mineralization. A longer durability is expected with the clinical use of the Mosaic porcine valve.

Topics: Animals; Bioprosthesis; Calcinosis; Cardiovascular Agents; Disease Models, Animal; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Mitral Valve; Models, Cardiovascular; Oleic Acid; Oleic Acids; Sheep

Vascular remodeling, often accelerated after cardiovascular procedures, may result in stenosis or aneurysm formation. The bone-associated protein osteopontin has been suggested to be involved in vascular remodeling, yet the effect of locally applied osteopontin in an acute vascular injury model of aortic calcification has not been examined.. Vascular healing of rabbit thoracic aortas treated locally with recombinant osteopontin (dose: 1 microg; n = 16) or albumin (control, n = 16) after acute injury created by end-to-end anastomosis was evaluated. Matrix metalloproteinase-2 level was quantified by gelatin zymography. Proliferation of smooth muscle cells was detected by immunostaining for proliferative cell nuclear antigen.. Osteopontin-treated aortas showed significantly diminished vascular remodeling with less calcification (P = .001) and reduced anastomotic luminal stenosis (4% vs 28%, P = .002) compared with controls 2 months postsurgery. Moreover, osteopontin-treated aortas revealed a thickened adventitia with increased fibrosis (P = .006). Matrix metalloproteinase-2 level was up-regulated 2-fold with osteopontin treatment compared with control at 1 week, returning to baseline by 1 month. Staining for proliferation cell nuclear antigen disclosed an increase in proliferation cell nuclear antigen-positive smooth muscle cells in the media of osteopontin-treated aortas at 1 week, normalizing by 1 month.. These data suggest a beneficial effect of locally applied osteopontin after acute injury possibly by altering matrix metalloproteinase-2 activity and smooth muscle cell proliferation. Brief application of osteopontin may effectively enhance vascular healing by reducing calcification and thus maintaining luminal integrity. The role of the osteopontin-related increase in adventitial fibrosis on vascular healing has to be explored.

Topics: Animals; Aorta, Thoracic; Calcinosis; Cardiovascular Agents; Constriction, Pathologic; Male; Matrix Metalloproteinase 2; Models, Animal; Osteopontin; Rabbits; Sialoglycoproteins; Vascular Diseases; Wound Healing

Topics: Adult; Calcinosis; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Fibrinolytic Agents; Humans; Hypolipidemic Agents; Kidney Failure, Chronic; Male; Renal Dialysis; Tomography, X-Ray Computed

Since calcium overload and increased in T-type calcium channel activity have been observed in the cardiomyopathic (CM) hamster, we hypothesized that mibefradil (Ro 40-5967), a new T- and L-type calcium channel blocker, may exert significant cardioprotection in the early phase of the disease. Young (30-day-old) CM hamsters of the UM-X7.1 subline were treated with mibefradil or verapamil for 4 to 6 weeks. Mibefradil doses were in the range of 0.5 to 8 mg/kg/day while verapamil was given at a dose of 5-10 mg/kg/day, both drugs being injected twice daily (s.c. and i.p. alternatively). At the end of the treatment period, myocardial and skeletal muscle (tongue) were harvested and processed for assessment of necrotic changes and calcification. In hearts from control CM hamsters, numerous necrotic and calcified foci were observed. These myocardial necrosis markers were not attenuated by mibefradil in the dose range studied whereas verapamil significantly reduced their severity. The dystrophic process in skeletal muscle (tongue) was not inhibited by mibefradil or verapamil. These results suggest that mechanisms other than inhibition of T- and L-type calcium channels are related to the cardioprotection observed in the presence of verapamil. A specific action on the sarcoplasmic reticulum (ryanodine-sensitive calcium channel) or the mitochondria may explain the efficacy of phenylalkylamines (verapamil) in this condition.

Topics: Animals; Biomarkers; Calcinosis; Calcium Channel Blockers; Cardiomyopathies; Cardiovascular Agents; Cricetinae; Female; Heart; Male; Mibefradil; Muscle, Skeletal; Myocardium; Necrosis; Time Factors; Tongue; Verapamil

A total of 502 patients presenting in Utsunomiya city and its suburbs during a 10-year period were studied to determine the clinical features of ischemic heart disease and to identify coronary risk factors. The male/female ratio was 1.21, but the ratio decreased with increasing age. The duration of chest pain showed a continuous spectrum between angina and infarction, with a short duration of chest pain not being useful for excluding the diagnosis of myocardial infarction. Hypertension was more common than hypercholesterolemia in this study, although the prevalence of the latter increased slightly with time, along with the shift towards a modernized occupational pattern. Smoking was a more important risk factor for ischemic heart disease in younger individuals than in the elderly, and diabetes mellitus was highly associated with the development of myocardial infarction. The incidence of radiologically diagnosed cardiac hypertrophy and aortic calcification decreased over time. These changes may have resulted in part from improved blood pressure control and the development of new anti-hypertensive and cholesterol-lowering agents.

Topics: Age Factors; Alcohol Drinking; Aortic Diseases; Arteriosclerosis; Calcinosis; Cardiomegaly; Cardiovascular Agents; Chest Pain; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Hypertension; Japan; Male; Morbidity; Myocardial Ischemia; Occupations; Risk Factors; Smoking; Urban Population