sirolimus and Ventricular-Dysfunction--Left

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

Cardiac remodeling and contractile dysfunction are leading causes in hypertrophy-associated heart failure (HF), increasing with a population's rising age. A hallmark of aged and diseased hearts is the accumulation of modified proteins caused by an impaired autophagy-lysosomal-pathway. Although, autophagy inducer rapamycin has been described to exert cardioprotective effects, it remains to be shown whether these effects can be attributed to improved cardiomyocyte autophagy and contractility. In vivo hypertrophy was induced by transverse aortic constriction (TAC), with mice receiving daily rapamycin injections beginning six weeks after surgery for four weeks. Echocardiographic analysis demonstrated TAC-induced HF and protein analyses showed abundance of modified proteins in TAC-hearts after 10 weeks, both reduced by rapamycin. In vitro, cardiomyocyte hypertrophy was mimicked by endothelin 1 (ET-1) and autophagy manipulated by silencing Atg5 in neonatal cardiomyocytes. ET-1 and siAtg5 decreased Atg5-Atg12 and LC3-II, increased natriuretic peptides, and decreased amplitude and early phase of contraction in cardiomyocytes, the latter two evaluated using ImageJ macro Myocyter recently developed by us. ET-1 further decreased cell contractility in control but not in siAtg5 cells. In conclusion, ET-1 decreased autophagy and cardiomyocyte contractility, in line with siAtg5-treated cells and the results of TAC-mice demonstrating a crucial role for autophagy in cardiomyocyte contractility and cardiac performance.

Topics: Animals; Animals, Newborn; Autophagy; Autophagy-Related Protein 5; Cardiomegaly; Echocardiography; Endothelin-1; Gene Silencing; Heart Failure; Male; Mice, Inbred C57BL; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Pressure; Sirolimus; TOR Serine-Threonine Kinases; Ventricular Dysfunction, Left; Ventricular Remodeling

Primary valvular heart disease is a prevalent cause of morbidity and mortality in both industrialized and developing countries. Although the primary consequence of valvular heart disease is myocardial dysfunction, treatment of valvular heart diseases centers around valve repair or replacement rather than prevention or reversal of myocardial dysfunction. This is particularly evident in primary mitral regurgitation (MR), which invariably results in eccentric hypertrophy and left ventricular (LV) failure in the absence of timely valve repair or replacement. The mechanism of LV dysfunction in primary severe MR is entirely unknown.. Here, we developed the first mouse model of severe MR. Valvular damage was achieved by severing the mitral valve leaflets and chords with iridectomy scissors, and MR was confirmed by echocardiography. Serial echocardiography was performed to follow up LV morphology and systolic function. Analysis of cardiac tissues was subsequently performed to evaluate valve deformation, cardiomyocyte morphology, LV fibrosis, and cell death. Finally, dysregulated pathways were assessed by RNA-sequencing analysis and immunofluorescence.. In the ensuing 15 weeks after the induction of MR, gradual LV dilatation and dysfunction occurred, resulting in severe systolic dysfunction. Further analysis revealed that severe MR resulted in a marked increase in cardiac mass and increased cardiomyocyte length but not width, with electron microscopic evidence of sarcomere disarray and the development of sarcomere disruption. From a mechanistic standpoint, severe MR resulted in activation of multiple components of both the mammalian target of rapamycin and calcineurin pathways. Inhibition of mammalian target of rapamycin signaling preserved sarcomeric structure and prevented LV remodeling and systolic dysfunction. Immunohistochemical analysis uncovered a differential pattern of expression of the cell polarity regulator Crb2 (crumbs homolog 2) along the longitudinal axis of cardiomyocytes and close to the intercalated disks in the MR hearts. Electron microscopy images demonstrated a significant increase in polysome localization in close proximity to the intercalated disks and some areas along the longitudinal axis in the MR hearts.. These results indicate that LV dysfunction in response to severe MR is a form of maladaptive eccentric cardiomyocyte hypertrophy and outline the link between cell polarity regulation and spatial localization protein synthesis as a pathway for directional cardiomyocyte growth.

Topics: Animals; Cell Adhesion Molecules; Cell Shape; Cell Size; Disease Models, Animal; Echocardiography; Fibrosis; Gene Expression Profiling; Hypertrophy; Infusion Pumps, Implantable; Magnetic Resonance Imaging; Male; Mice; Mitral Valve; Mitral Valve Insufficiency; Myocytes, Cardiac; Polyribosomes; RNA, Messenger; Sirolimus; Systole; TOR Serine-Threonine Kinases; Ventricular Dysfunction, Left

Long-term clinical outcomes of new-generation drug-eluting stents in complex anatomic and clinical settings are not well defined. This study assessed the impact of patient and lesion complexity on 2-year outcomes after coronary revascularization with ultrathin strut biodegradable-polymer (BP) sirolimus-eluting stents (SES) versus durable-polymer (DP) everolimus-eluting stents (EES). In a prespecified analysis of the BIOSCIENCE randomized trial (NCT01443104), complex patients (911 of 2,119; 43%) were defined by the presence of acute ST-elevation myocardial infarction (MI); left ventricular ejection fraction ≤30%; renal dysfunction; insulin-treated diabetes; treatment of ostial lesion, bypass graft, unprotected left main lesion; or 3-vessel intervention. The primary end point was target lesion failure (TLF), a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization. At 2 years, complex compared with simple patients had a greater risk of TLF (14.5% vs 7.4%, risk ratio 2.05, 95% confidence interval 1.56 to 2.69; p <0.001). The difference was sustained beyond 1 year on landmark analysis. Complex patients had higher rates of the patient-oriented composite end point of death, any MI, or any revascularization (23% vs 14.4%; p <0.001) as well as definite stent thrombosis (1.6% vs 0.4%, p = 0.006). There were no differences in TLF and patient-oriented composite end point between the BP-SES versus DP-EES, consistently among simple and complex patients. In conclusion, patient and lesion complexity had a durable adverse impact on clinical outcomes throughout 2 years of follow-up in this all-comers randomized trial. Safety and efficacy of new-generation BP-SES and DP-EES were comparable, irrespective of complexity status.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Comorbidity; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Percutaneous Coronary Intervention; Polymers; Prognosis; Prospective Studies; Prosthesis Design; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Severity of Illness Index; Sirolimus; ST Elevation Myocardial Infarction; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

The endoplasmic reticulum (ER) plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH).. ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs). Myocardial mechanical and intracellular Ca(2+) properties, ER stress, autophagy and associated cell signaling molecules were evaluated.. ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca(2+) homeostasis), oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62), along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene.. Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy.

Topics: Adenine; Alcohol Dehydrogenase; Animals; Autophagy; Calcium; Endoplasmic Reticulum Stress; MAP Kinase Signaling System; Mice; Mice, Inbred Strains; Mice, Transgenic; Myocardial Contraction; Myocardium; Oxidative Stress; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Recombinant Fusion Proteins; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Transgenes; Tunicamycin; Ultrasonography; Ventricular Dysfunction, Left

Everolimus drug-eluting stents (EES) are superior to early-generation drug-eluting stents (DES), releasing sirolimus (SES) or paclitaxel (PES) in preventing stent thrombosis (ST). Since an impaired LVEF seems to increase the risk of ST, we aimed to investigate the difference in outcome of patients with varying LVEF using EES versus early-generation DES.. In a prospective cohort study, we compared the risk of ST in patients in three LVEF subgroups: normal (LVEF >50%), mildly impaired (LVEF >40% and ≤50%) and moderate-severely impaired (LVEF ≤40%). Within these various LVEF groups, we compared EES with SES and PES after adjustment for baseline differences.. We assessed a cohort of 5363 patients, with follow-up of up to 4 years and available LVEF. Overall definite ST occurred in 123 (2.3%) patients. ST rates were higher in the LVEF moderate-severely impaired group compared with the normal LVEF group (2.8% vs 2.1%; HR 1.82; CI 1.10 to 3.00). Especially early ST (EST) was more frequent in the moderate-severely impaired LVEF group (HR 2.20; CI 1.06 to 4.53). Overall rates of definite ST were lower in patients using EES compared with patients using SES or PES in all LVEF groups. Interaction terms were not statistically significant. ST rates were higher in the moderate-severely impaired LVEF group compared with the normal LVEF group when using SES or PES, but not significantly different when using EES.. EES was associated with a lower risk of definite ST compared with early-generation DES. This lower risk was independent of LVEF, even though ST rates were higher in patients with a moderate-severely impaired LVEF.. MEC-2013-262.

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Incidence; Kaplan-Meier Estimate; Percutaneous Coronary Intervention; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Severity of Illness Index; Sirolimus; Stroke Volume; Switzerland; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

We present a case of a bifurcation lesion treated with two dedicated sirolimus eluting bifurcation stents, BiOSS Lim in the setting of non-ST elevation myocardial infarction and poor left ventricular function. We demonstrate the feasibility of a new technique, a "simplified" culotte technique. The key differences of this new technique compared with conventional culotte are: better sizing of the stent due to the specific design of the stent with a larger proximal diameter and smaller distal diameter, direct stenting of the second stent without predilatation of the stent struts of the first deployed stent, and possibility to perform post-dilatation directly with properly sized balloons without additional predilatation.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Stenosis; Drug-Eluting Stents; Electrocardiography; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Prosthesis Design; Risk Assessment; Sirolimus; Treatment Outcome; Ventricular Dysfunction, Left

Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of these in cardiac function and cardiomyocyte death is unclear. We report that rapamycin, an mTOR inhibitor, restored cardiac function in a passively β1-AAB-immunized rat model with decreased cardiac function and myocardial autophagic flux. Next, after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, β1-AAB-induced autophagy was an initial protective stress response before apoptosis. Then, decreased autophagy contributed to cardiomyocyte death followed by decreases in cardiac function. In conclusion, proper regulation of autophagy may be important for treating patients with β1-AAB-positive heart dysfunction.

Topics: Adenine; Adrenergic beta-1 Receptor Antagonists; Animals; Apoptosis; Apoptosis Regulatory Proteins; Autoantibodies; Autophagy; Beclin-1; Cardiomyopathies; Cell Line; Gene Expression Regulation; Humans; Immunization, Passive; Male; Myocytes, Cardiac; Rats; Rats, Wistar; Receptors, Adrenergic, beta-1; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Ventricular Dysfunction, Left; Ventricular Pressure

To investigate the entire process of autophagy in the left ventricle of septic mice, and the functional significance of autophagy by using pharmacological agents.. Myocardial dysfunction is a common feature in sepsis and contributes to an increased risk of developing multiple organ failure. Autophagy functions predominantly as a prosurvival pathway in the heart during cellular stress. A dynamic process of autophagy that involves the complete activation of autophagy from autophagosome formation to fusion with lysosomes has driven the development of new approaches to detecting autophagy.. Male mice were subjected to cecal ligation and puncture (CLP) or sham operation. At 1 hour after CLP operation, mice received either rapamycin (induction of autophagy), bafilomycin A1 (inhibition of autophagosomal degradation), or vehicle.. The formation of autophagosomes was increased whereas the degradation of autophagosomes was decreased in the left ventricle at 24 hours after CLP. This was consistent with the morphologic finding that septic hearts revealed an increase in autophagosomes but few autolysosomes, indicating incompletion of the autophagic process. Rapamycin, which induced complete activation of autophagy, restored CLP-induced depressed cardiac performances. This cardioprotective effect was also seen in increased ATP levels, and decreased inflammatory responses. Bafiomycin A1, which resulted in incompletion of the autophagic process, did not show any above beneficial effects in CLP mice.. Incompletion of the autophagic process may contribute to sepsis-induced cardiac dysfunction. Treatment with rapamycin may serve a cardioprotective role in sepsis, possibly through the effect of complete induction of autophagy.

Topics: Animals; Autophagy; Disease Models, Animal; Heart Ventricles; Immunosuppressive Agents; Male; Mice; Mice, Inbred C3H; Sepsis; Sirolimus; Ventricular Dysfunction, Left

Sirolimus-eluting stent (SES) implantation aggravated endothelial vasomotor dysfunction in infarct-related coronary arteries.. This study examined the effect of SES implantation on the duration of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and on postinfarct left ventricular dysfunction in acute myocardial infarction (AMI). Patients with a first AMI due to occlusion of the left anterior descending coronary artery and successful reperfusion using SES (n=15) or bare metal stents (BMS; n=18) were examined. The vasomotor response of the left anterior descending coronary artery to acetylcholine and left ventriculography were examined 2 weeks and 6 months after AMI. At 6 months after AMI, the impairment of epicardial coronary artery dilation and coronary blood flow increase in response to acetylcholine was recovered from 2 weeks after AMI in BMS-treated patients, whereas the responses of SES-treated patients improved but remained impaired compared with BMS-treated patients (% increase in blood flow, 77+/-12% in SES versus 116+/-15% in BMS at 10 microg/min of acetylcholine, P<0.01). Left ventricular regional wall dysfunction in the left anterior descending coronary artery territory improved from 2 weeks to 6 months after AMI in BMS-treated patients but not in SES-treated patients (% improvement of average SD/chord, 6% in SES versus 19% in BMS, P<0.05), although left ventricular global ejection fraction was similar between the groups at any time points.. SES implantation may delay recovery of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and left ventricular regional dysfunction for at least 6 months after AMI.

Topics: Aged; Anti-Bacterial Agents; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Regional Blood Flow; Retrospective Studies; Sirolimus; Stroke Volume; Time Factors; Ventricular Dysfunction, Left

The extent of adverse myocardial remodeling contributes essentially to the prognosis after myocardial infarction (MI). In this study we investigated whether inhibition of "mammalian target of rapamycin" (mTOR) attenuates left ventricular (LV) remodeling after MI.. Therapeutic strategies to inhibit remodeling are currently limited to inhibition of neurohumoral activation. The mTOR-dependent signaling mechanisms are centrally involved in remodeling processes and provide new therapeutic opportunities.. Everolimus (RAD) treatment was initiated on the day after or 3 days after induction of myocardial infarction (MI) in rats.. After 28 days, RAD-treated animals had reduced post-MI remodeling, with improved LV function and smaller LV end-diastolic diameters (8.9 + or - 0.3 mm vs. 11.4 + or - 0.2 mm, p < 0.05), end-diastolic volumes (304 + or - 30 microl vs. 414 + or - 16 microl, p < 0.05), and cardiac myocyte size (-40% vs. vehicle, p < 0.05). Infarct size was significantly reduced compared with vehicle-treated animals. The mTOR inhibition increased autophagy and concomitantly decreased proteasome activity in the border zone of the infarcted myocardium. Measurement of autophagic flux demonstrated that RAD did not decrease autophagosome clearance. When RAD treatment was initiated 3 days after MI, adverse remodeling was still attenuated and increased autophagy was still present. Sustained improvement of LV function was observed 3 months after MI, even when RAD treatment was discontinued after 1 month.. Inhibition of mTOR is a potential therapeutic strategy to limit infarct size and to attenuate adverse LV remodeling after MI.

Topics: Animals; Atrial Natriuretic Factor; Autophagy; Diastole; Echocardiography; Everolimus; Heart Ventricles; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Male; Microtubule-Associated Proteins; Myocardial Infarction; Myocytes, Cardiac; NF-kappa B; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Wistar; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus; TOR Serine-Threonine Kinases; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Remodeling

Recent studies have reported a higher incidence of late stent thrombosis in patients undergoing drug-eluting stent (DES). Reduced left ventricular (LV) ejection fraction (EF) is considered a risk factor for this complication after both bare-metal stent (BMS) and DES implantation. Therefore, the aim of this study was to evaluate the safety of DES on long-term follow-up in patients with LV dysfunction undergoing percutaneous coronary intervention. We retrospectively selected all patients with an EF <45% undergoing percutaneous coronary intervention with implantation of > or =1 sirolimus- or paclitaxel-eluting stent at our institution. The primary endpoint of the study was all-cause mortality, retrieved using both Social Security Database and hospital records. We also compared the results of this group with a historical cohort of patients with LV dysfunction undergoing BMS implantation; 121 patients who received > or =1 DES were enrolled. The mean LVEF was 36 +/- 8%, with 20 patients (16%) with a LVEF < or =25%; 36 patients (30%) had diabetes mellitus, and DES implantation was considered off-label in 100 patients (83%). Survival at 1-, 2-, and 3-year follow-up was 94% (95% confidence interval [CI] 88 to 100), 90% (95% CI 82 to 98) and 88% (95% CI 80 to 96), respectively. In conclusion, the favorable results of this study demonstrate the safety of DES in patients with LV dysfunction.

Topics: Adrenergic beta-Antagonists; Angioplasty, Balloon, Coronary; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Paclitaxel; Retrospective Studies; Sirolimus; Stroke Volume; Survival Analysis; Ventricular Dysfunction, Left

Topics: Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Bypass; Humans; Myocardial Ischemia; Paclitaxel; Patient Selection; Prosthesis Design; Radiography; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

We compared the outcome of drug eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction with the outcome of a similar group of patients undergoing coronary artery by-pass grafting (CABG).. Revascularization provides long-term benefits in patients with severe LV dysfunction. However the modality to achieve it is still unsettled in this high risk group of patients.. Two-hundred-twenty patients (20% women) with severe LV dysfunction (LV Ejection Fraction

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Bypass; Female; Follow-Up Studies; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Retrospective Studies; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; United States; Ventricular Dysfunction, Left

We examined the efficacy of drug-eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction and compared the outcome with a similar group of patients undergoing bare metal stent (BMS) implantation.. Patients with severe LV dysfunction are a high risk group. DES may improve the long term outcomes compared with BMS.. One hundred and ninety one patients (23% women) with severe LV dysfunction (LV ejection fraction < or =35%) underwent coronary stent implantation between May 2002 and May 2005 and were available for follow-up. One hundred and twenty eight patients received DES (Sirolimus in 72 and Paclitaxel in 54) and 63 patients had BMS. Patients with acute S-T elevation myocardial infarction (STEMI) were excluded. The primary endpoint was cardiovascular mortality. A composite endpoint of major adverse cardiac events (MACE) including cardiovascular mortality, myocardial infarction (MI), and target vessel revascularization (TVR) was the secondary endpoint.. Mean follow-up was 420 +/- 271 days. No differences were noted in age (69 +/- 10 years vs. 70 +/- 10 years, P = NS), number of vessel disease (2.3 +/- 0.7 vs. 2.2 +/- 0.8, P = NS), history of congestive heart failure (47% vs. 46%, P = NS), MI (60% vs. 61%, P = NS), or number of treated vessels (1.3 +/- 0.5 vs. 1.3 +/- 0.6, P = NS) for the DES and BMS group, respectively. Diabetes was more common among DES patients (45% vs. 25%, P = 0.01). The left ventricular ejection fraction (LVEF) was similar between the two groups (28% +/- 6% vs. 26% +/- 8%, P = NS for the DES and BMS, respectively). During the follow-up, there were a total of 25 deaths of which two were cancer related (2 in DES group). There were 23 cardiac deaths, 8/126 (6%) which occurred in the DES group and 15/63 (24%) in the BMS group (P = 0.05 by log-rank test). MACE rate was 10% for the DES group and 41% for the BMS group (P = 0.003). NYHA class improved in both groups (from 2.5 +/- 0.8 to 1.7 +/- 0.8 in DES and from 2 +/- 0.8 to 1.4 +/- 0.7 in the BMS, P = NS).. Compared with bare-metal stents, DES implantation reduces mortality and MACE in high risk patients with severe left ventricular dysfunction.

Topics: Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Cardiomyopathies; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Severity of Illness Index; Sirolimus; Stents; Stroke Volume; Survival Rate; Treatment Outcome; United States; Ventricular Dysfunction, Left

Multiple overlapping drug-eluting stents have increasingly been used to treat diffuse coronary disease, but the safety and efficacy of this approach remains unclear. We assayed the clinical and angiographic outcomes after placement of "full metal jacket" stents (stented length >or=60 mm) in 347 consecutive patients (352 lesions) with very long de novo coronary lesions. Mean age was 61.0 +/- 10.1 years, and the mean stented length was 71.9 +/- 13.7 mm. The procedural success rate was 97.7%. Major in-hospital complications (1 death, 2 cases of acute stent thrombosis) occurred in 3 patients (0.7%). Angiographic follow-up data, obtained for 230 (234 lesions) of the 328 eligible patients (70.1%), showed that the restenosis rate was 13.7%. Multivariate analysis found that the reference artery diameter (odds ratio 0.05, 95% confidence interval [CI] 0.01 to 0.33, p = 0.002) and the use of Taxus stents (odds ratio 2.88, 95% CI 1.03 to 8.04, p = 0.043) were significant predictors of restenosis. During follow-up (16.6 +/- 6.9 months), 9 deaths (6 cardiac and 3 noncardiac), 1 nonfatal myocardial infarction, and 13 target lesion revascularizations occurred. The cumulative probability of survival without major adverse cardiac events (cardiac death, Q-wave myocardial infarction, and target lesion revascularization) was 95.4 +/- 1.1% and 91.4 +/- 2.1% at 1 and 2 years, respectively. Left ventricular dysfunction (ejection fraction <45%) was the only predictor of stent thrombosis (hazard ratio 18.24, 95% CI 1.65 to 201.19, p = 0.018) and cardiac death/Q-wave myocardial infarction (hazard ratio 5.37, 95% CI 1.28 to 22.49, p = 0.021). In conclusion, full metal jacket drug-eluting stents may be a safe and effective method to treat diffuse coronary disease and may be a useful treatment option for complex long lesions.

Topics: Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Korea; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Outcome Assessment, Health Care; Paclitaxel; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Ventricular Dysfunction, Left

Although target lesion revascularization (TLR) has been dramatically decreased by using drug-eluting stents (DESs) in de-novo lesions, their efficacy for in-stent restenosis (ISR) has not yet been well established.. We retrospectively analysed patients treated for ISR with DESs from three referral hospitals.. Eighty-seven consecutive patients, from June 2002 to April 2004, were included, with a mean age of 64+/-11 years; 83% were men, 32% had diabetes, 47% had had a previous myocardial infarction and 16% had low left ventricular ejection fraction. Angiographic characteristics were as follows: mean vessel diameter, 3.05+/-0.4 mm; lesion length, 17.8+/-7.7 mm; diameter stenosis, 84.0+/-10.7%; and complex lesion, 81%. The restenosis was focal in 45%, diffuse/proliferative in 51.3% and total occlusion in 3.7% of the cases. Sirolimus- and paclitaxel-eluting stents were used in 42 and 58% of the patients, respectively. Stent diameter was 3.1+/-0.3 mm and the length was 26.1+/-5.8 mm. Angiographic success was achieved in all patients, with one patient experiencing a post-procedural non-Q-wave myocardial infarction. At 6-month clinical follow-up, two patients had died from non-cardiac deaths, five had experienced a new TLR (5.7%, four percutaneous and one coronary artery bypass graft) and eight (9.2%) had had major adverse cardiac events. A stress test was performed in 60% of the population; target vessel ischemia was observed in one patient (3.3%).. In this non-select cohort of patients, the use of DESs is a safe and effective strategy for ISR lesions.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Practice Patterns, Physicians'; Retrospective Studies; Sirolimus; Stents; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left

We performed this study in order to compare the immediate and mid-term outcomes of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in lesions of the unprotected left main coronary artery (LMCA). We assessed 54 patients from 5 centers who had undergone unprotected LMCA stenting (35 SES and 19 PES). The procedural success rates were 100 and 95%, respectively, in the SES and PES patients (p = 0.19). At the 6-month clinical follow-up, the event-free probability was 100% in the SES group, and 88% in the PES group (p = 0.07). At the 6-month angiographic follow-up (n = 24), the SES group exhibited a slightly lower late loss than did the PES group (0.24 +/- 0.44 vs. 0.65 +/- 0.60 mm, p = 0.09), and the restenosis rates were 8 and 9% (p = 0.94) in the SES and PES patients, respectively. In conclusion, both groups exhibited excellent in-hospital and 6-month outcomes with no significant differences between them.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Stents; Treatment Outcome; Ventricular Dysfunction, Left