sirolimus and Rupture--Spontaneous

Statins are currently able to stabilize atherosclerotic plaques by lowering plasma cholesterol and pleiotropic effects, but a residual risk for atherosclerotic disease remains. Therefore, effective prevention of atherosclerosis and treatment of its complications is still a major clinical challenge. A large body of evidence indicates that mammalian target of rapamycin (mTOR) inhibitors such as rapamycin or everolimus have pleiotropic anti-atherosclerotic effects so that these drugs can be used as add-on therapy to prevent or delay the pathogenesis of atherosclerosis. Moreover, bioresorbable scaffolds eluting everolimus trigger a healing process in the vessel wall, both in pigs and humans, that results in late lumen enlargement and plaque regression. At present, this phenomenon of atheroregression is poorly understood. However, given that mTOR inhibitors suppress cell proliferation and trigger autophagy, a cellular survival pathway and a process linked to cholesterol efflux, we hypothesize that these compounds can inhibit (or reverse) the basic mechanisms that control plaque growth and destabilization. Unfortunately, adverse effects associated with mTOR inhibitors such as dyslipidemia and hyperglycemia have recently been identified. Dyslipidemia is manageable via statin treatment, while the anti-diabetic drug metformin would prevent hyperglycemia. Because metformin has beneficial macrovascular effects, this drug in combination with an mTOR inhibitor might have significant promise to treat patients with unstable plaques. Moreover, both statins and metformin are known to inhibit mTOR via AMPK activation so that they would fully exploit the beneficial effects of mTOR inhibition in atherosclerosis.

Topics: Absorbable Implants; AMP-Activated Protein Kinases; Animals; Apolipoproteins E; Cholesterol; Clinical Trials as Topic; Coronary Artery Disease; Drug Evaluation, Preclinical; Drug Interactions; Drug Therapy, Combination; Drug-Eluting Stents; Dyslipidemias; Everolimus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Macrophages; Metformin; Mice; Mice, Knockout; Plaque, Atherosclerotic; Rabbits; Receptors, LDL; Rupture, Spontaneous; Sirolimus; Swine; Tissue Scaffolds; TOR Serine-Threonine Kinases; Triglycerides

Spontaneous coronary artery dissection is an unusual condition that mainly happens in fit and healthy women in the peripartum period. Strenuous exercise is a rare cause of dissection in angiographically normal coronary arteries. There is no definitive consensus on the etiology, prognosis and treatment of SCAD. We report a case of successful treatment of a late presentation of a coronary artery dissection secondary to intense physical activity in a 48 year old cyclist who continued to cycle for 3 months post event.

Topics: Angioplasty, Balloon, Coronary; Bicycling; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Exercise; Female; Follow-Up Studies; Humans; Middle Aged; Rupture, Spontaneous; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Coronary stent infection is exceedingly rare despite the widespread use of percutaneous coronary intervention (PCI). The utilization of drug-eluting stents (DES) may have a higher theoretical risk of infection due to their local immunosuppressant effect. Vigilance in suspecting stent infection is important, as the associated mortality rate is approximately 50%. We discuss the case of a patient who presented with an infected DES 2 weeks after implantation which led to spontaneous Type II coronary perforation. The perforation was sealed with prolonged balloon inflation, and the patient was treated with intravenous antibiotics. This is the first reported case of a patient with a stent infection who presented with a spontaneous coronary perforation.

Topics: Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Drug-Eluting Stents; Echocardiography; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Prosthesis-Related Infections; Rupture, Spontaneous; Sirolimus; Staphylococcal Infections

This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI).. There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age.. In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography.. Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up.. In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Health Status Disparities; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Rupture, Spontaneous; Sex Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Anastomosis, Surgical; Carcinoma, Hepatocellular; Disease Progression; Fatal Outcome; Female; Hematoma; Hepatic Artery; Humans; Immunosuppressive Agents; Liver Neoplasms; Middle Aged; Patient Readmission; Peritoneal Cavity; Postoperative Care; Reoperation; Risk Assessment; Rupture, Spontaneous; Sirolimus; Tacrolimus; Tomography, X-Ray Computed

To compare vascular healing after drug-eluting stent (DES) implantation between plaque rupture (PR) and plaque erosion (PE).. Vascular response after stent implantation in patients with PR has been extensively studied. Little is known about vascular healing after stent implantation in PE.. Sixty-five ACS patients who received optical coherence tomography (OCT) imaging of the culprit lesions both before and after stent implantation at baseline as well as at 6 months were included in this study. Patients were divided into two groups: PR (n = 19) and PE (n = 24). Prestent thrombus burden and poststent intrastent structure (ISS) volume were analyzed during the index procedure. The ratio of uncovered to total stent struts per cross-section score (RUTTS) and neointimal thickness and area were measured at follow-up.. OCT imaging showed that compared with PR, PE showed a significantly lower prestent thrombus score (34.2 ± 19.2 vs. 68.6 ± 44.2, P = 0.009) at baseline and a smaller poststent ISS volume (0.7 ± 0.9 mm. PE was associated with less favorable healing following DES implantation when compared to PR at 6 months, indicating longer dual-antiplatelet therapy may be necessary for patients with PE. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Occlusion; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prosthesis Design; Rupture, Spontaneous; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Aged; Drug-Eluting Stents; Humans; Male; Rupture, Spontaneous; Sirolimus; Vascular Calcification

Spontaneous pyopneumothorax is a very rare occurrence, even in cancer treated patients. Here we present two consecutive cases of spontaneous pyopneumothorax that occurred early after initiation of mTOR inhibitors for the treatment of renal cell carcinoma with subpleural pulmonary metastasis. In these two cases, necrosis and excavation of lung metastasis were observed, suggesting their involvement in the pathogenic mechanism of pyopneumothorax. This report extends the available experience of the pulmonary side effects of these novel targeted therapies.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Calcitonin; Carcinoma, Renal Cell; Combined Modality Therapy; Disease Susceptibility; Everolimus; Fatal Outcome; Female; Humans; Indoles; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Necrosis; Neoplasm Proteins; Nephrectomy; Niacinamide; Phenylurea Compounds; Pneumonia, Bacterial; Pneumothorax; Protein Precursors; Pyridines; Pyrroles; Rupture, Spontaneous; Sirolimus; Sorafenib; Sunitinib; TOR Serine-Threonine Kinases