sirolimus and Heart-Diseases

We evaluated the impact of the everolimus-eluting stent (EES) on the frequency of stent thrombosis (ST), target vessel revascularization (TVR), myocardial infarction (MI), and cardiac death in randomized controlled trials comparing the EES to non-everolimus-eluting drug-eluting stents (EE-DES).. Whether or not the unique properties of the EES translate into reductions in ST remains unknown.. We searched MEDLINE, Scopus, the Cochrane Library, and Internet sources for articles comparing outcomes between EES and non-EE-DES without language or date restriction. Randomized controlled trials reporting the frequency of ST were included. Variables relating to patient and study characteristics and clinical endpoints were extracted.. We identified 13 randomized trials (n = 17,101) with a weighted mean follow-up of 21.7 months. Compared with non-EE-DES, the EES significantly reduced ST (relative risk [RR]: 0.55; 95% confidence interval [CI]: 0.38 to 0.78; p = 0.001), TVR (RR: 0.77; 95% CI: 0.64 to 0.92; p = 0.004), and MI (RR: 0.78; 95% CI: 0.64 to 0.96; p = 0.02). There was no difference in cardiac mortality between the groups (RR: 0.92; 95% CI: 0.74 to 1.16; p = 0.38). The treatment effect was consistent by different follow-up times and duration of clopidogrel use. The treatment effects increased with higher baseline risks of the respective control groups with the strongest correlation observed for ST (R(2) = 0.89, p < 0.001).. Intracoronary implantation of the EES is associated with highly significant reductions in ST with concordant reductions in TVR and MI compared to non-EE-DES. Whether these effects apply to different patient subgroups and DES types merits further investigation.

Topics: Aged; Drug-Eluting Stents; Everolimus; Female; Heart Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Randomized Controlled Trials as Topic; Sirolimus; Thrombosis; Treatment Outcome

The use of immunosuppression regimens containing a calcineurin inhibitor (CNI), an adjunct immunosuppressant (e.g., azathioprine, everolimus or mycophenolate mofetil) and corticosteroids has effectively reduced the risk of early graft loss due to acute rejection in heart transplant recipients. At present, late graft loss due to cardiac allograft vasculopathy (CAV) remains a major challenge for transplant teams. CAV is characterized by intimal hyperplasia as a result of endothelial cell injury. Factors relating to the transplant procedure itself (e.g., ischemic time and reperfusion injury), cardiovascular risks (e.g., donor age, hypertension, hyperlipidemia, pre-existing diabetes and new-onset diabetes after transplantation), immunologic risks (e.g., acute rejection episodes, anti-HLA antibodies) and the side effects of immunosuppression with CNIs or corticosteroids (e.g., cytomegalovirus infection, nephrotoxicity) have all been implicated in the development of CAV. The 2 main approaches to the prevention of CAV are modification of underlying risk factors (e.g., treatment with anti-hypertensive agents and lipid-lowering drugs, and optimizing the immunosuppressive regimen) and improvement in immunosuppression. CNIs remain the cornerstone of immunosuppressive regimens in heart transplantation, but new parameters for monitoring CNI exposure and new immunosuppressive regimens hold the promise of reduced overall CNI exposure with consequent reductions in vascular toxicity and improved clinical outcomes. Traditionally, trough levels of cyclosporine (C(0)) have been used to monitor exposure to cyclosporine and to assess the need for dose adjustment. However, optimal cyclosporine exposure can now be achieved through monitoring of cyclosporine levels 2 hours after dosing (C(2) monitoring). Furthermore, in a pivotal trial in heart transplantation, the new proliferation signal inhibitor, everolimus, plus full-dose cyclosporine and corticosteroids, has been shown to have improved impact on prevention of biopsy-proven acute rejection (and other efficacy end-points) and longer term on the prevention of CAV. In addition, there is evidence from studies in renal transplant recipients that everolimus plus reduced exposure cyclosporine is effective and well tolerated-with the regimen having a reduced potential for CNI-related nephrotoxicity and for other CNI-related cardiovascular side effects.

Topics: Adrenal Cortex Hormones; Azathioprine; Calcineurin Inhibitors; Cyclosporine; Dose-Response Relationship, Drug; Everolimus; Heart Diseases; Heart Transplantation; Humans; Immunosuppressive Agents; Mycophenolic Acid; Sirolimus

The wide variation in bifurcation anatomy has generated an ongoing search for stents explicitly designed for coronary bifurcations, and to date, results have been underachieved.. The POLBOS I and POLBOS II were international, multicentre, randomized, open-label, controlled trials. Patients were randomly assigned to BiOSS Expert (in POLBOS I, biodegradable polymer eluting paclitaxel)/BiOSS LIM (in POLBOS II, biodegradable polymer eluting sirolimus) stent implantation or regular drug-eluting stent (rDES) deployment. A provisional T-stenting strategy was the default treatment option. The primary endpoint of this pooled data study was the cumulative rate of major adverse cardiovascular events (MACE) consisting of cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). Telephone follow-up was performed annually up to 72 months. (ClinicalTrials.gov Identifier: POLBOS I-NCT02192840, POLBOS II-NCT02198300).. The total study population consisted of 445 patients, 222 patients in the BiOSS group and 223 patients in the rDES group. The follow-up rate was 93.7% in the BiOSS group and 91.9% in the rDES group. At 72 months, there was no significant difference between BiOSS and rDES groups regarding MACE (25.7% vs 25.1%, HR 1.06, 95% CI 0.73-1.52), cardiac death (3.1% vs 4.0%, HR 0.94, 95% CI 0.43-2.34), MI (3.6% vs 4.9%, HR 0.76, 95% CI 0.32-2.89), TLR (18.9% vs 16.1%, HR 1.17, 95% CI 0.75-1.83) and stent thrombosis rates (0.9% vs 0.5%, HR 1.21, 95CI 0.75-2.09).. At the 6-year follow-up, clinically significant clinical events did not differ between BiOSS stents and rDES.

Topics: Absorbable Implants; Aged; Coronary Vessels; Drug-Eluting Stents; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Sirolimus

Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited.. In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority.. A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority).. Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

Topics: Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Heart Diseases; Hemorrhage; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Prosthesis Design; Single-Blind Method; Sirolimus

Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.

Topics: Adult; Allografts; Calcineurin Inhibitors; Cyclosporine; Drug Therapy, Combination; Everolimus; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Heart Diseases; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Prognosis; Risk Factors; Sirolimus; Transplant Recipients; Vascular Diseases

The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).. The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the "all-comers" LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046).. The SXscore when applied to an "all-comers" patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Heart Diseases; Humans; Male; Middle Aged; Polymers; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Cyclosporine (CsA) is widely used after heart transplantation. The purpose of this prospective randomized study was to evaluate the safety and efficacy of reduction of CsA blood level to one-half of the traditional blood concentration under a regimen of everolimus (EVL), CsA, and steroid.. This prospective, 6 month, randomized, open-label study included adult (aged 18 to 65 years) recipients of a primary heart transplant with serum creatinine60 years old, had cold ischemia time>6 hours, or had plasma renin activity>or=25%. All patients received CsA (C2 blood level 1000-1400 ng/mL), EVL (C0 target 3-8 ng/mL), and corticosteroids to day 60, before random entry into one of 2 groups: SE (C2 blood level from days 60-149=800-1200 ng/mL, and days 150-180 C2=600-1000 ng/mL), or RE group with CsA reduced by one-half after 3 months (days 90-149 C2=400-600 ng/mL, and from days 150-180 C2=300-500 ng/mL).. The 25 recipients eligible for this study included 13 patients in the SE and 12 in the RE group. There was no operative mortality in either group. No death or graft loss was noted within 6-months in either group. Mean serum creatinine at month 6 tended to be lower in the RE cohort (1.23+/-0.44 mg/dL versus 1.55+/-0.85 mg/dL; P=.093). Biopsy-proven acute rejection>or=grade 3A was observed in only 1 patient (7.7%), who was in the SE group. There were no acute rejection episodes associated with hemodynamic compromise. The incidences of adverse events in each group were similar.. Concentration-controlled EVL (C0 target 3-8 ng/mL) in combination with reduced CsA exposure of one-half the usual concentration achieved good efficacy and safety over 6 months. The renal function at 6 months among the RE group showed a trend toward improvement, suggesting a benefit of halving the target CsA blood level after heart transplantation.

Topics: Adolescent; Adult; Aged; Creatinine; Cyclosporine; Dose-Response Relationship, Drug; Everolimus; Female; Heart Diseases; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Function Tests; Male; Middle Aged; Patient Selection; Sirolimus; Tissue Donors; Young Adult

The efficacy of sirolimus-eluting stents (SESs) has not been established in dialysis patients.. This study was a non-randomized observational single-center registry in a community hospital: data for 80 consecutive dialysis patients who underwent percutaneous coronary intervention (PCI) with SES were compared with those of a historical group of consecutive 124 dialysis patients treated with bare-metal stents (BMS). After 1 year, the cumulative incidence of major adverse cardiac events (MACE), comprising cardiac death, nonfatal myocardial infarction, stent thrombosis, or target lesion revascularization (TLR), was 25.2% in the SES group and 38.2% in the BMS group (p=0.048). In multivariate analysis, use of SES remained an independent predictor of MACE at 1 year after PCI (risk ratio 0.70, 95% confidence interval 0.52-0.93, p=0.015). Rates of TLR were 21.7% in the SES group and 30.9% in the BMS group and (p=0.15). Subgroup analysis showed that use of SES was effective in patients with small vessels, non-diabetic patients, and patients without highly calcified lesions.. In dialysis patients, the implantation of SES was moderately effective in reducing MACE at 1 year after PCI as compared with BMS. However, the TLR rate at 1 year was relatively higher than previously reported.

Topics: Aged; Cardiac Catheterization; Drug-Eluting Stents; Female; Heart Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Renal Dialysis; Sirolimus; Time Factors

Left ventricular hypertrophy (LVH) and diastolic dysfunction occur after cardiac transplantation. We investigated sirolimus (SRL) as primary immunosuppression for the attenuation of LVH and diastolic dysfunction of the cardiac allograft.. Seventy cardiac transplant recipients were converted to SRL, 5.79+/-3.90 years after transplant, with complete calcineurin-inhibitor (CNI) withdrawal. Three consecutive echocardiographic studies, 1 year apart, were analyzed for changes in left ventricular (LV) mass and diastolic function during CNI and SRL treatment.. Changes in systolic (P=0.69) and diastolic blood pressures (BP) (P=0.32) did not differ between SRL and CNI treatment. LV mass and LV mass index increased (185.03+/-41.59-197.21+/-47.39 g, P=0.033 and 94.20+/-18.64-98.93+/-20.08 g/m; P=0.030) during CNI and decreased (197.21+/-47.39-187.59+/-48.88 g, P=0.025 and 98.93+/-20.08-94.06+/-20.31 g/m P=0.050) during SRL. The difference in Delta LV mass and Delta LV mass index was significant (P=0.011 and P=0.017, respectively) and was not associated with changes in BP. Left atrium volume index increased during CNI (46.73+/-16.3 5-54.20+/-18.47 cm/m, P=0.006) and decreased during SRL (54.20+/-18.47-49.75+/-18.40 cm/m, P=0.0036). The difference in left atrium (Delta LA) volume index was significant (P=0.002) and was not associated with changes in BP.. Withdrawal of CNI and replacement with SRL in cardiac transplant recipients results in a decrease in LV mass and improvement in diastolic function. SRL may be useful to attenuate LVH and improve cardiac allograft diastolic function.

Topics: Adult; Aged; Calcineurin Inhibitors; Cardiomyopathies; Diastole; Echocardiography; Female; Follow-Up Studies; Heart Diseases; Heart Transplantation; Hemodynamics; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Systole; Transplantation, Homologous; Ventricular Dysfunction, Left; Ventricular Function, Left

The aims of this study were to assess (i) the feasibility, safety and efficacy of sirolimus-eluting stents (SESs) in treating in-stent restenosis (ISR), (ii) the risk factors for recurrent ISR, and (iii) the long-term major adverse cardiac events (MACE).. Between May 2002 and April 2004, 100 consecutive patients with evidence of myocardial ischaemia and 112 ISRs in native coronary arteries were treated using SESs. We evaluated the rate of procedural and clinical success, the incidence of in-hospital and long-term MACE, the recurrence rate of ISR after 6-8 months, and the risk factors for recurrent ISR and follow-up MACE.. Forty-five percent of the lesions were directly stented. After stent implantation, the minimal lumen diameter increased from 0.51 +/- 0.32 to 2.50 +/- 0.32 mm in the stents and to 2.30 +/- 0.35 mm in the lesions (acute gain 1.99 +/- 0.37 mm). The procedural success rate was 99%. The clinical success rate was 88%. MACE occurred in 2.0% of patients during hospitalisation and in 12.8% after a median follow-up of 15.1 months (interquartile range 8.4-19.7). The recurrence rate of ISR was 11.8% after a median follow-up of 7.7 months (interquartile range 7.4-8.4). The risk for recurrent ISR was significantly higher in patients with diabetes or hypertension, in those aged more than 65 years and in female patients, as well as in the lesions with a small minimal lumen diameter. Three-vessel disease and age were risk factors for MACE.. This study confirms the feasibility, safety and effectiveness of using SESs to treat ISR, and identifies a risk profile for recurrent ISR and MACE.

Topics: Coronary Restenosis; Drug Delivery Systems; Feasibility Studies; Female; Follow-Up Studies; Heart Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Risk Factors; Sirolimus; Stents; Treatment Outcome

The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown.. Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. Consecutive patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting stents (SES group) were compared with 450 patients who received bare stents in the period just before (pre-SES group). Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62 [95% CI, 0.44 to 0.89]; P=0.008). The 1-year risk of clinically driven target vessel revascularization in the SES group and in the pre-SES group was 3.7% versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P<0.001).. Unrestricted utilization of sirolimus-eluting stents in the "real world" is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Female; Heart Diseases; Humans; Male; Netherlands; Registries; Sirolimus; Stents; Treatment Outcome

Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Autophagy-Related Protein-1 Homolog; Creatine Kinase, MM Form; Cyclic N-Oxides; Electron Transport Complex IV; GTPase-Activating Proteins; Heart Diseases; Mechanistic Target of Rapamycin Complex 1; Mice; Muscular Diseases; Myocardium; Oxidative Stress; Peptide Initiation Factors; Polyesters; Ribosomal Protein S6 Kinases; Sequestosome-1 Protein; Sirolimus; Spin Labels; Succinate Dehydrogenase; Superoxides; Tuberous Sclerosis Complex 1 Protein; Ubiquitinated Proteins

Cardiac rhabdomyoma is the most common cardiac tumour in childhood, with a strong genetic association to tuberous sclerosis complex. Although most of the patients remain asymptomatic, a small proportion present with cardiac complications in the early neonatal period. Timely initiation of treatment can potentially reduce disease morbidity, and mammalian target of rapamycin (M-TOR) inhibitors play an effective role in promoting regression of these tumours. A healthy term newborn was diagnosed with a giant congenital cardiac rhabdomyoma at birth. He developed clinical signs of compromised cardiac function and progressive myocardial ischaemia, with echocardiography showing significant dyskinesia. He was treated with M-TOR inhibitors and clinical response was monitored via serial echocardiography. Remarkable regression of the tumour was visibly demonstrated within 4 months of sirolimus treatment. The infant continues to be reviewed by a multidisciplinary team of physicians and monitored for features of tuberous sclerosis complex.

Topics: Female; Heart Diseases; Heart Neoplasms; Humans; Infant; Infant, Newborn; Male; Rhabdomyoma; Sirolimus; Tuberous Sclerosis

Data on the long-term effects of everolimus (EVL) on the de novo immunosuppression of heart transplant (HT) recipients with progressive cardiac allograft vasculopathy (CAV) and vascular remodeling are lacking. Hence, in this study, we aimed to determine the long-term safety and efficacy of EVL as a de novo immunosuppressant therapy for CAV progression and the clinical outcomes after HT.. We retrospectively reviewed the medical records of 144 HT recipients who survived for at least one year after HT. CAV progression was assessed via serial coronary intravascular ultrasonography (IVUS) in recipients who underwent at least two IVUS studies.. A significant attenuation in the percentage of the atheroma volume progression was observed in those who took EVL (1.2%) compared with those who took cyclosporin (CSA; 7.3%; p = 0.005 vs. EVL) or tacrolimus (TAC; 6.6%; p = 0.0052 vs. EVL) at 1 year after HT. This trend persisted for the next 3 and 5 years after HT. Moreover, the remodeling index was greater in the EVL (1.08) group than in the CSA (0.23) or TAC (-0.25) groups 1 year after HT. The results of the Kaplan-Meier analysis over a median follow-up period of 8 years revealed that there was no statistical difference in the primary endpoint between the three groups.. De novo immunosuppression with EVL is associated with attenuated CAV progression for the first 5 years of follow-up via IVUS. Moreover, EVL has comparable long-term clinical outcomes to those of CSA- or TAC-based protocols.

Topics: Allografts; Everolimus; Follow-Up Studies; Heart Diseases; Heart Transplantation; Humans; Immunosuppressive Agents; Retrospective Studies; Sirolimus; Ultrasonography, Interventional

Topics: Angiotensin II; Animals; Autophagy; DNA, Mitochondrial; Heart Diseases; Heart Injuries; Hypertension; Mice; Microglia; Nucleotidyltransferases; Paraventricular Hypothalamic Nucleus; Sirolimus

This study was designed to confirm in a large population of unselected patients the promising results of Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) already shown in previous trial.. ULISSE is an observational, multicenter, national registry evaluating all patients undergoing PCI with the Ultimaster® BP-SES. Incidence of 1-year TLF (cardiac death or target vessel MI or clinically indicated TLR) was the primary endpoint. Pre-specified subgroup analysis was performed for diabetic patients and for those with lesion longer than 25 mm, bifurcation and CTO lesions.. 1660 patients were enrolled in 9 Italian cardiology centers, 82% were males, mean age of 68 ± 10 years, and 29% were diabetics. Overall 2422 lesions were treated, 65% type B2/C lesions, 7% CTOs, 17% bifurcations and 38% long lesions. The incidence of 1-year TLF was 5%, with 3.2% of clinically indicated TLR. TLF occurred in 8% of the patients with diabetes mellitus, and 7% in bifurcation, 6.7% in CTO and 6.2% in long lesions. Definite overall ST was 0.9%, and 1.2% in patients treated for type B2/C lesions. Multivariate logistic regression analysis identified stenting on unprotected LMT (OR = 4.80), stenting on ISR lesion (OR = 3.19) and need for rotational atherectomy (OR = 6.24) as the strongest independent predictors of TLF.. The results of this national all-comers registry show that the Ultimaster® BP-SES real-world performance was comparable with that observed in the clinical trial, with low rate of primary endpoint and TLR. Long term follow-up will be necessary to prove the theoretical advantage of the BP-SES over time.

Topics: Absorbable Implants; Aged; Anti-Bacterial Agents; Death; Drug-Eluting Stents; Female; Follow-Up Studies; Heart Diseases; Humans; Italy; Male; Middle Aged; Population Surveillance; Registries; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

Kaposiform hemangioendothelioma (KHE) is a rare and aggressive vascular tumor that can be associated with a consumptive coagulopathy and thrombocytopenia (Kasabach-Merritt phenomenon). Only one case of an intracardiac KHE has been reported which was treated with surgical excision and then expectant management.. We present a patient with an intracardiac KHE which presented as a large mass surrounding the atria, pulmonary veins, superior vena cava, and infiltrating the atrial septum with moderate compression of the superior vena cava and mild compression of the pulmonary veins. This tumor clinically presented as persistent tachypnea and was unresponsive to conventional therapy with vincristine and steroids but responded dramatically to Sirolimus with almost complete regression on follow-up.. None of the current treatments for KHE, alone or in combination therapy have been found to be effective in a uniform or reproducible manner. Well designed, preferably randomized trials are required for a better understanding of the appropriate dosage and duration as well as response to treatment and a consensus of first and second line therapies.

Topics: Heart Diseases; Hemangioendothelioma; Humans; Infant; Kasabach-Merritt Syndrome; Pulmonary Veins; Salvage Therapy; Sarcoma, Kaposi; Sirolimus; Steroids; Tachypnea; Vincristine

This study evaluated the safety and efficacy of the RESOLUTE(TM)zotarolimus-eluting stent (R-ZES; Medtronic, Inc, Santa Rosa, CA, USA) in Japanese patients for the treatment of de novo native coronary lesions.. Both RESOLUTE Japan (R-Japan) and RESOLUTE Japan Small Vessel Study (R-Japan SVS) were prospective, multicenter, single-arm observational studies. R-Japan enrolled 100 patients (reference vessel diameter, 2.5-3.5 mm) and R-Japan SVS enrolled 65 patients (at least 1 lesion suitable for 2.25-mm stent) treated with R-ZES. In R-Japan, in-stent late lumen loss (LLL; the primary endpoint) at 8 months was 0.12 ± 0.22 mm and volume obstruction on intravascular ultrasound was 2.33 ± 3.51%. At 4 years, there were no cases of clinically driven target lesion revascularization (TLR); the target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, and clinically driven TLR) was 5.6% (5/90). In R-Japan SVS, in-stent LLL at 9 months was 0.27 ± 0.33 mm, TLF (primary endpoint) was 4.6% (3/65), without incidence of TLR. At 3 years, TLF was 7.9% (5/63) and clinically driven TLR, 3.2% (2/63).. R-Japan and R-Japan SVS demonstrate substantial suppression of neointimal hyperplasia, low LLL, and excellent and sustained long-term clinical outcome with R-ZES in Japanese patients.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Heart Diseases; Humans; Incidence; Japan; Myocardial Infarction; Myocardial Revascularization; Neointima; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Risk Factors; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Triptolide (TP), a major bioactive component isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF), has been shown to exert various pharmacological effects. However, the severe toxicity of TP prevents wide clinical use. In a previous study, we reported that TP-induced mitochondria-dependent apoptosis in cardiomyocytes is mediated by reactive oxygen species (ROS). Autophagy is a cellular self-digestion process and is one of the first lines of defense against oxidative stress. Additionally, recent evidence suggests that autophagy can selectively eliminate damaged mitochondria. This study investigated the role of autophagy in TP-induced cardiotoxicity. We investigated the effects of autophagy in combination with TP on apoptosis, ROS and mitochondrial function. Rat cardiomyocytes were pre-treated with chloroquine or rapamycin followed by TP. The augmentation of autophagy with rapamycin in the presence of TP substantially ameliorated the detrimental effects induced by TP, while suppression of autophagy by chloroquine accelerates TP-induced cellular damage. In addition, pre-treated with rapamycin before TP administration also attenuated TP-induced damage in Balb/c mice heart tissues. Taken together, these results suggest that TP-induced cell death can be modified by autophagy. Furthermore, induction of autophagy by rapamycin may be a potential cardioprotective role against TP-induced cardiotoxicity by facilitating removal of dysfunctional mitochondria.

Topics: Animals; Apoptosis; Autophagy; Cell Line; Diterpenes; Epoxy Compounds; Heart Diseases; Mice; Mice, Inbred BALB C; Myocytes, Cardiac; Phenanthrenes; Rats; Sirolimus

Diabetes mellitus (DM) is an independent risk factor for heart disease and its underlying mechanisms are unclear. Increased expression of diabetic marker miR-29 family miRNAs (miR-29a, b and c) that suppress the pro-survival protein Myeloid Cell Leukemia 1(MCL-1) is reported in pancreatic β-cells in Type 1 DM. Whether an up-regulation of miR-29 family miRNAs and suppression of MCL-1 (dysregulation of miR-29-MCL-1 axis) occurs in diabetic heart is not known. This study tested the hypothesis that insulin regulates cardiac miR-29-MCL-1 axis and its dysregulation correlates with DM progression. In vitro studies with mouse cardiomyocyte HL-1 cells showed that insulin suppressed the expression of miR-29a, b and c and increased MCL-1 mRNA. Conversely, Rapamycin (Rap), a drug implicated in the new onset DM, increased the expression of miR-29a, b and c and suppressed MCL-1 and this effect was reversed by transfection with miR-29 inhibitors. Rap inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling in HL-1 cells. Moreover, inhibition of either mTORC1 substrate S6K1 by PF-4708671, or eIF4E-induced translation by 4E1RCat suppressed MCL-1. We used Zucker diabetic fatty (ZDF) rat, a rodent model for DM, to test whether dysregulation of cardiac miR-29-MCL-1 axis correlates with DM progression. 11-week old ZDF rats exhibited significantly increased body weight, plasma glucose, insulin, cholesterol, triglycerides, body fat, heart weight, and decreased lean muscle mass compared to age-matched lean rats. Rap treatment (1.2 mg/kg/day, from 9-weeks to 15-weeks) significantly reduced plasma insulin, body weight and heart weight, and severely dysregulated cardiac miR-29-MCL1 axis in ZDF rats. Importantly, dysregulation of cardiac miR-29-MCL-1 axis in ZDF rat heart correlated with cardiac structural damage (disorganization or loss of myofibril bundles). We conclude that insulin and mTORC1 regulate cardiac miR-29-MCL-1 axis and its dysregulation caused by reduced insulin and mTORC1 inhibition increases the vulnerability of a diabetic heart to structural damage.

Topics: Animals; Blood Glucose; Diabetes Complications; Gene Expression Regulation; Heart Diseases; Humans; Insulin; Insulin-Secreting Cells; Mechanistic Target of Rapamycin Complex 1; Mice; MicroRNAs; Multiprotein Complexes; Myeloid Cell Leukemia Sequence 1 Protein; Myocytes, Cardiac; Rats; Sirolimus; TOR Serine-Threonine Kinases

The BASE-ACS trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) that was statistically non-inferior to that of everolimus-eluting stents (EES) at 12-month follow-up, in patients presenting with acute coronary syndrome (ACS) who underwent early percutaneous coronary intervention (PCI). We explored a post-hoc analysis of the 12-month outcome of the BASE-ACS trial in the subgroup of patients with ST-elevation myocardial infarction (STEMI) versus non-ST-elevation ACS (non-STEACS).. A total of 827 patients with ACS (321 STEMI) were randomly assigned to receive either BAS or EES. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) at 12-month follow-up.. The 12-month cumulative incidence of the primary endpoint was similar between the two subgroups (9% versus 9.5%, in STEMI versus non-STEACS patients respectively, P=0.90). The 12-month rate of cardiac death was significantly higher in the STEMI subgroup as compared with the non-STEACS subgroup (2.8 versus 0.6%, respectively, P=0.01). However, the rates of non-fatal MI, ischemia-driven TLR, definite stent thrombosis, and non-cardiac death were all statistically matched between the two subgroups (P>0.05 for all).. In the current post-hoc analysis of the BASE-ACS trial based on the infarction type, the 12-month outcome of patients who underwent early PCI for ACS was slightly worse in the setting of STEMI as compared with non-STEACS, as reflected by a significantly higher rate of cardiac death.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Coated Materials, Biocompatible; Combined Modality Therapy; Coronary Restenosis; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Heart Diseases; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Sirolimus; Titanium; Treatment Outcome

With newer drug-eluting stents (DES), PCI has appeared as an acceptable alternative to cardiac surgery in the treatment of unprotected left main (ULM) lesions. Using data from the French Left Main Taxus and the LEft MAin Xience registries, we compared two-year outcomes in consecutive patients from 2003-2008 using everolimus-eluting stents (EES) vs. paclitaxel-eluting stents (PES).. We performed a matched comparison according to SYNTAX score, distal LM stenosis, provisional side-branch T-stenting and single stent use, focusing on the primary endpoints of target vessel MI (TVMI) and target vessel failure (TVF). After propensity score matching, there were 172 patients in each group. There was no difference in gender (76.5% male), age (69.5 ± 11.3 years), diabetes (26.2% vs. 24.4%, p=0.71), NSTEMI (40.7% vs. 40.7%, p=1), or LVEF <40% (11.0% vs. 6.7%, p=0.22). Patients with distal LM lesions (75.9%) were treated using provisional T-stenting in 91.1%. The side branch was stented in 22% of all patients (p=0.51). Cumulative two-year events showed significant differences in TVMI (9.9% vs. 4.1%, p=0.04) and TVF (16.3% vs. 7.6%, p=0.01) for PES and EES, respectively.. ULM stenting with EES is safer and more effective than PES with a reduction in TLF by 53% at two years.

Topics: Aged; Aged, 80 and over; Drug-Eluting Stents; Everolimus; Female; Heart Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Propensity Score; Registries; Sirolimus; Treatment Outcome

Decreases in cardiac Na/K-ATPase have been documented in patients with heart failure. Reduction of Na/K-ATPase α1 also contributes to the deficiency in cardiac contractility in animal models. Our previous studies demonstrate that reduction of cellular Na/K-ATPase causes cell growth inhibition and cell death in renal proximal tubule cells. To test whether reduction of Na/K-ATPase in combination with increased cardiotonic steroids causes cardiac myocyte death and cardiac dysfunction, we examined heart function in Na/K-ATPase α1 heterozygote knock-out mice (α1(+/-)) in comparison to wild type (WT) littermates after infusion of marinobufagenin (MBG). Adult cardiac myocytes were also isolated from both WT and α1(+/-) mice for in vitro experiments. The results demonstrated that MBG infusion increased myocyte apoptosis and induced significant left ventricle dilation in α1(+/-) mice but not in their WT littermates. Mechanistically, it was found that in WT myocytes MBG activated the Src/Akt/mTOR signaling pathway, which further increased phosphorylation of ribosome S6 kinase (S6K) and BAD (Bcl-2-associated death promoter) and protected cells from apoptosis. In α1(+/-) myocytes, the basal level of phospho-BAD is higher compared with WT myocytes, but MBG failed to induce further activation of the mTOR pathway. Reduction of Na/K-ATPase also caused the activation of caspase 9 but not caspase 8 in these cells. Using cultures of neonatal cardiac myocytes, we demonstrated that inhibition of the mTOR pathway by rapamycin also enabled MBG to activate caspase 9 and induce myocyte apoptosis.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Bufanolides; Caspase 8; Caspase 9; Cells, Cultured; Enzyme Activation; Enzyme Inhibitors; Heart Diseases; Mice; Mice, Mutant Strains; Muscle Proteins; Myocytes, Cardiac; Proto-Oncogene Proteins c-akt; Signal Transduction; Sirolimus; Sodium-Potassium-Exchanging ATPase; src-Family Kinases; TOR Serine-Threonine Kinases

Topics: Coronary Disease; Data Interpretation, Statistical; Drug-Eluting Stents; Heart Diseases; Humans; Sirolimus; Stents

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

Endothelial progenitor cell (EPC) capture stent is designed to promote rapid endothelization and healing and is potentially useful in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We studied the intermediate-term efficacy and safety of EPC stent and compared that with sirolimus-eluting bioabsorbable polymer stent (CURA) and bare metal stent (BMS) in AMI patients.. Patients presenting with AMI who underwent primary PCI with the respective stents between January 2004 and June 2006 were enrolled in the single-center clinical registry. The study end-points were major adverse cardiac events (MACE) and stent thrombosis.. A total of 366 patients (EPC = 95, CURA = 53, BMS 218) were enrolled. Baseline demographics including age, gender, diabetes, renal impairment, predischarge left ventricular ejection fraction, and creatinine kinase level were comparable among the groups. Procedural success rate was 99.5%. Post-procedural thrombolysis in myocardial infarction (TIMI) 3 flow was achieved in EPC 91.6%, CURA 96.2%, and BMS 88.5% (P = 0.209). At 2 years, the MACE rate was EPC 13.7%, CURA 15.1%, and BMS 19.7% (P = 0.383). Target vessel revascularizations (TVR) were EPC 4.2%, CURA 9.4%, and BMS 6.0% (P = 0.439). Nonfatal myocardial infarctions were EPC 1.1%, CURA 3.8%, and BMS 4.1% (P = 0.364). One patient in the EPC group had acute stent thrombosis. There was no late stent thrombosis in the EPC group.. EPC stent appeared to be safe and had comparable clinical efficacy with a BMS when used in the AMI setting. At 2-year follow-up, the EPC group showed favorable, single-digit TVR rate and stent thrombosis remained a low-event occurrence.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Bioengineering; Coated Materials, Biocompatible; Cohort Studies; Drug-Eluting Stents; Electrocardiography; Endothelial Cells; Equipment Design; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Registries; Sirolimus; Stem Cells; Stents; Thrombosis; Treatment Outcome

This study aimed to evaluate the impact of angiographic and intravascular ultrasound (IVUS) features on clinical outcome in nondiabetic and type 2 diabetic patients after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation.. Repeat coronary angiography with IVUS imaging was performed after SES-based PCI for de-novo lesions in 128 diabetic and 327 nondiabetic patients (189 lesions and 504 lesions, respectively). The rate of major adverse cardiac events including cardiac death, non fatal myocardial infarction (MI), and target lesion revascularization during clinical follow-up was recorded.. In-stent and in-segment late loss, intimal hyperplasia volume, and percentage volumetric obstruction were similar, but stented external elastic membrane cross-sectional area and reference/stented segment ratio were lower in diabetic than in nondiabetic patients. Incomplete stent apposition (ISA) was less frequent, but occurrence of new coronary lesions was higher in diabetic than in nondiabetic patients. Despite similar target lesion revascularization, cumulative survival rates freedom from composite cardiac death and nonfatal MI or major adverse cardiac events were reduced in diabetic patients. Cox proportional hazards model identified diabetes, left ventricular ejection fraction, minimal stent CSA, maximal ISA area, atherosclerotic progression and lesion length as independent predictors of non fatal MI or mortality at follow-up.. In diabetic patients, PCI with SES implantation neutralizes the excess risk of intimal hyperplasia and decreases occurrence of ISA, but could not modify the propensity of increased adverse clinical outcomes at follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Heart Diseases; Humans; Hyperplasia; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The aim of this study was to determine which drug-eluting stent (DES) is preferable for the treatment of ST-segment elevation myocardial infarction (STEMI) and to elucidate the impact of diabetes mellitus on the outcome of each DES.. Recent studies have shown the benefit of DES in patients with STEMI. Diabetes mellitus might differentially affect outcomes of each DES.. We analyzed the large-scale, prospective, observational KAMIR (Korea Acute Myocardial Infarction Registry) study, which enrolled 4,416 STEMI patients (26% with diabetes) treated with paclitaxel-eluting stent (PES) or sirolimus-eluting stent (SES). Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization (TLR).. In the overall population, the MACE rate at 1 year was significantly higher in the PES than the SES group (11.6% vs. 8.6%, p = 0.014), which was mainly due to increased TLR (3.7% vs. 1.8%, p < 0.001). In the diabetic subgroup, however, the MACE rate was not significantly different between PES and SES (14.5% vs. 12.3%, p = 0.217), in contrast to the nondiabetic subgroup, where PES was inferior to SES as in the overall population. Matching by propensity-score did not significantly alter these results. For TLR, there was interaction between the type of stents and diabetes mellitus (unadjusted: p = 0.052; after propensity-score matching: p = 0.035).. The PES was inferior to the SES in the overall population, with regard to the occurrence of MACE and TLR. However, subgroup analysis for diabetic subjects showed no differences in clinical outcomes between PES and SES. These results suggest that diabetes differentially affects the outcome of first-generation DES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Diabetes Complications; Drug-Eluting Stents; Female; Heart Diseases; Humans; Korea; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Propensity Score; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Recurrence; Registries; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Long-term clinical outcomes of diabetes mellitus (DM) patients who underwent drug-eluting stent deployment has not well investigated.. A total of 2,050 cases were enrolled consecutively from 50 sites in Japan into the Cypher stent Japan Post-Marketing Surveillance (Cypher J-PMS) registry, and the 3-year outcomes of DM patients were analyzed. Subjects were divided into 2 groups based on the treatment of DM (insulin-treated diabetes (IT) group, n=207; and non insulin-treated diabetes (NIT) group, n=682). Major adverse cardiac event (MACE) rates in the IT group and the NIT group were 26.0% and 14.5% at 3 years, respectively (P<0.001). There were no significant differences in stent thrombosis rates (definite and probable by Academic Research Consortium (ARC) definition) (0% and 1.08%, respectively). Multivariate analysis suggested that hemodialysis and insulin-treated DM were independent predictors for MACE, and insulin-treated DM, hemodialysis and long lesions were strong independent predictors for target-lesion revascularization (TLR).. Hemodialysis and insulin-treated DM were strong independent predictors of mortality and TLR in DM patients. These results might suggest that special attention to patients with hemodialysis and insulin-treated DM is warranted in the setting of sirolimus-eluting stent deployment for DM patients.

Topics: Aged; Diabetes Complications; Drug-Eluting Stents; Female; Follow-Up Studies; Heart Diseases; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Japan; Male; Middle Aged; Product Surveillance, Postmarketing; Registries; Renal Dialysis; Sirolimus; Thrombosis; Time Factors

Drug-eluting stents (DES) have been demonstrated to dramatically reduce the rate of in-stent restenosis (ISR). However, some studies found an increased rate of late incomplete stent apposition (ISA) and late stent thrombosis (ST) in DES compared to traditional bare-metal stents (BMS). Endeavor stent, a new cobalt-alloy DES coated with phosphorylcholine and zotarolimus, has been reported to have a very favorable safety profile with few documented late-acquired ISA and late ST. In the present report, we described an interesting case with coexistent ISR, late ISA and mural thrombus in an Endeavor zotarolimus-eluting stent 8 months after primary percutaneous coronary intervention.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Heart Diseases; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Prosthesis Failure; Reoperation; Sirolimus; Thrombosis; Ultrasonography, Interventional

Topics: Clinical Trials as Topic; Drug-Eluting Stents; Heart Diseases; Humans; Platelet Aggregation Inhibitors; Sirolimus; Treatment Outcome; United States; United States Food and Drug Administration

Everolimus (Certican; Novartis Pharma AG, Basel, Switzerland) represents the latest generation of proliferation signal inhibitors (PSIs). Everolimus is indicated for use as an immunosuppressive drug in renal and heart transplantation. This report reflects the recommendations of the second German-Austrian Certican Consensus Conference, held in January 2006, for the clinical use of everolimus.

Topics: Angioedema; Coronary Disease; Drug Interactions; Drug Monitoring; Everolimus; Heart Diseases; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Lipids; Lung Diseases, Interstitial; Renal Insufficiency; Sirolimus; Skin Diseases; Transplantation, Homologous; Wound Healing

The central role of phosphatidylinositol 3-kinase (PI3K, p110alpha) signaling in allowing cancer cells to bypass normal growth-limiting controls has led to the development of PI3K(p110alpha) inhibitors. A challenge in targeting PI3K(p110alpha) relates to the diverse actions of the PI3K pathway in numerous cell types. Recent findings in mice deficient in PI3K(p110alpha) activity in the heart, demonstrate the critical role of this pathway in protecting the heart against pathological insults. Mice deficient in PI3K(p110alpha) displayed accelerated heart failure in response to dilated or hypertrophic cardiomyopathy. These results help explain the association of cardiomyopathy in cancer patients given tyrosine kinase inhibitors and raise concerns for the use of PI3K(p110alpha) inhibitors in cancer patients with cardiovascular risk factors. Interestingly, an inhibitor of the mammalian target of rapamycin (a downstream effector of PI3K), did not have adverse effects on the heart. A more complete understanding of the complex arms and interactions of the PI3K pathway will hopefully lead to the development of anti-cancer agents without cardiac complications.

Topics: Animals; Antineoplastic Agents; Class I Phosphatidylinositol 3-Kinases; Enzyme Inhibitors; Heart; Heart Diseases; Humans; Mice; Mice, Transgenic; Models, Biological; Neoplasms; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinases; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases

The authors aimed to compare the clinical outcomes with repeat drug-eluting stent (DES) implantation utilizing the same type versus an alternate DES type for in-stent restenosis (ISR) of DES.. : DES are proven as an effective treatment for bare metal ISR.. A cohort of 116 patients previously treated with a sirolimus-eluting stent (SES) or a paclitaxel-eluting stent (PES) who presented with angiographic ISR were treated with repeat DES. Of these, 62 (53.4%) were treated with different DES and 54 (46.6%) were treated with the same DES. This cohort was followed for clinical events at 30 days, 6 months, and 1 year.. Baseline characteristics were similar except for more diabetes among patients receiving the different type of DES. Of the 116, overall 16.4% of the DES were implanted for previous ISR and 2.6% had previously received brachytherapy. At 6 months, the overall target vessel revascularization (TVR) rate was 12.2% for the entire cohort. The TVR-major adverse cardiac event (MACE) rate for the patients treated with different DES was 14.5% and 16.7% for the same DES (P = 0.750). Overall TVR rate at 1 year was 28.8%. The TVR-MACE was 32.6% for different DES and 35.0% for the same DES (P = 0.814).. Reimplantation of DES for the treatment of DES ISR (same or different) is safe but associated with a high rate of recurrences at 1 year regardless of the initial DES type. Other treatment modalities for ISR of DES should be considered to further improve the overall TVR-MACE.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Heart Diseases; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Paclitaxel; Prosthesis Design; Reoperation; Secondary Prevention; Sirolimus; Stents; Time Factors; Treatment Outcome

This study evaluated the clinical and angiographic effectiveness of sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) implantation for chronic total occlusion (CTO) lesions.. It has not been known which drug-eluting stent, SES vs. PES, is superior for the treatment of CTO lesions.. This study comprises 107 CTO lesions which were successfully treated with SES implantation and 29 CTO lesions with PES implantation. Six-month angiographic restenosis rates and major adverse cardiac events (MACE) including death, nonfatal myocardial infarction and target lesion revascularization were compared between the two groups.. Baseline clinical characteristics were similar between the two groups. The procedural success rate was 98.1% in the SES group and 100% in the PES group. There was 1 sudden death due to in-hospital acute thrombosis in the PES group. There were no significant differences in baseline angiographic measures between both groups, except larger postprocedural minimal luminal diameter and acute gain in the PES group. At 6-month angiographic follow up, the restenosis rate was significantly higher in the PES group (28.6% vs. 9.4%; p = 0.020). Similarly, the late loss was significantly higher in the PES group (0.8 +/- 0.8 mm vs. 0.4 +/- 0.8 mm; p = 0.025). At one-year follow up, the MACE-free survival rate was significantly higher in the SES group (95.8% vs. 85.8%; p = 0.049).. The implantation of SES in the treatment of CTO lesions showed more favorable results regarding restenosis and clinical outcomes compared with PES implantation.

Topics: Adult; Chronic Disease; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Follow-Up Studies; Heart Diseases; Humans; Inpatients; Male; Middle Aged; Paclitaxel; Retrospective Studies; Sirolimus; Stents; Survival Analysis; Treatment Outcome

Topics: Heart Diseases; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Thrombectomy; Thrombosis

Topics: Blood Vessel Prosthesis; Coated Materials, Biocompatible; Combined Modality Therapy; Controlled Clinical Trials as Topic; Coronary Artery Bypass; Evidence-Based Medicine; Heart Diseases; Humans; Immunosuppressive Agents; Multicenter Studies as Topic; Sirolimus; Stents