sirolimus and Atrial-Fibrillation

The coronavirus disease 2019 (COVID-19) has affected approximately 2 million individuals worldwide; however, data regarding fatal cases have been limited.. To report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30, 2019 and March 12, 2020.. The demographic data, signs and symptoms, clinical course, comorbidities, laboratory findings, computed tomographic (CT) scans, treatments, and complications of the patients with fatal cases were retrieved from electronic medical records.. Young patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes. The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan.

Topics: Adolescent; Adult; Animals; Asthma; Atrial Fibrillation; Autoantibodies; Biomarkers; Breast Neoplasms; Child; Conjunctivitis, Allergic; Cornea; COVID-19; Cyclosporine; Cytokines; Death, Sudden, Cardiac; Defibrillators, Implantable; Diet; Disease Models, Animal; Docetaxel; Double-Blind Method; Dry Eye Syndromes; Educational Status; Emulsions; Female; Fluorescein Angiography; Fluoresceins; Focus Groups; Heart Failure; Hemothorax; Humans; Inflammation; Keratoconus; Male; Meibomian Glands; Mice; Middle Aged; Multiple Sclerosis; Myocardial Infarction; Myocardium; Nerve Fibers; Nigeria; Obesity; Overweight; Pandemics; Primary Prevention; Prospective Studies; Qualitative Research; Registries; Retinal Ganglion Cells; Retinal Vessels; Schools; Sirolimus; Tertiary Care Centers; Th1 Cells; Th2 Cells; Tomography, Optical Coherence; Troponin I; Tumor Necrosis Factor-alpha; United States; Ventricular Remodeling

The coronavirus disease 2019 (COVID-19) has affected approximately 2 million individuals worldwide; however, data regarding fatal cases have been limited.. To report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30, 2019 and March 12, 2020.. The demographic data, signs and symptoms, clinical course, comorbidities, laboratory findings, computed tomographic (CT) scans, treatments, and complications of the patients with fatal cases were retrieved from electronic medical records.. Young patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes. The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan.

Topics: Adolescent; Adult; Animals; Asthma; Atrial Fibrillation; Autoantibodies; Biomarkers; Breast Neoplasms; Child; Conjunctivitis, Allergic; Cornea; COVID-19; Cyclosporine; Cytokines; Death, Sudden, Cardiac; Defibrillators, Implantable; Diet; Disease Models, Animal; Docetaxel; Double-Blind Method; Dry Eye Syndromes; Educational Status; Emulsions; Female; Fluorescein Angiography; Fluoresceins; Focus Groups; Heart Failure; Hemothorax; Humans; Inflammation; Keratoconus; Male; Meibomian Glands; Mice; Middle Aged; Multiple Sclerosis; Myocardial Infarction; Myocardium; Nerve Fibers; Nigeria; Obesity; Overweight; Pandemics; Primary Prevention; Prospective Studies; Qualitative Research; Registries; Retinal Ganglion Cells; Retinal Vessels; Schools; Sirolimus; Tertiary Care Centers; Th1 Cells; Th2 Cells; Tomography, Optical Coherence; Troponin I; Tumor Necrosis Factor-alpha; United States; Ventricular Remodeling

Pulmonary vein (PV) stenosis (PVS) is a complication of radiofrequency PV isolation (PVI). Reported restenosis rates after balloon dilatation and bare-metal stent implantation are high. Drug-eluting stent implantation (DES) has not been reported in the setting of PVS.. Patients suspected of having PVS after PVI based on clinical symptoms and transesophageal echocardiography (TEE) follow-up (FU) were referred for PV DES. One or more branches of the affected PV as documented by angiography were stented (paclitaxel or zotarolimus DES). Follow-up consisted of repeat PV angiography and TEE. Over a period of 2 years, five patients were treated with a total of eight DES. A paclitaxel DES was used in seven of eight implants. Mean FU was 12 ± 14 months during which all patients remained asymptomatic. Transesophageal echocardiography Doppler maximal flow velocity (V(max)) of the affected PVs rose from 58 ± 6 cm/s pre-PVI to 207 ± 20 cm/s pre-DES (+358%, P < 0.0001). After DES, V(max) decreased acutely with 86 ± 15 cm/s (-58%, P < 0.01). During FU, V(max) remained stable in three patients and increased moderately in one. Angiography at 3 months confirmed absence of restenosis in the first three patients and moderate (40%) restenosis in one patient. In one patient, an increase of V(max) back to pre-DES values correlated with a 65% peri-stent stenosis, treated with a redo DES. In total, after seven primary DES only one (asymptomatic) proximal margin restenosis required re-stenting.. Initial experience with DES for PV stenosis suggests an excellent stent patency rate. Transesophageal echocardiography Doppler measurements provide a viable way of monitoring stent patency.

Topics: Adult; Aged; Atrial Fibrillation; Catheter Ablation; Constriction, Pathologic; Drug-Eluting Stents; Echocardiography, Transesophageal; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Paclitaxel; Pulmonary Veins; Retrospective Studies; Secondary Prevention; Sirolimus; Treatment Outcome; Vascular Diseases

LKB1 encodes a serine/threonine kinase, which functions upstream of the AMP-activated protein kinase (AMPK) superfamily. To clarify the role of LKB1 in heart, we generated and characterized cardiac myocyte-specific LKB1 knock-out (KO) mice using alpha-myosin heavy chain-Cre deletor strain. LKB1-KO mice displayed biatrial enlargement with atrial fibrillation and cardiac dysfunction at 4 weeks of age. Left ventricular hypertrophy was observed in LKB1-KO mice at 12 weeks but not 4 weeks of age. Collagen I and III mRNA expression was elevated in atria at 4 weeks, and atrial fibrosis was seen at 12 weeks. LKB1-KO mice displayed cardiac dysfunction and atrial fibrillation and died within 6 months of age. Indicative of a prohypertrophic environment, the phosphorylation of AMPK and eEF2 was reduced, whereas mammalian target of rapamycin (mTOR) phosphorylation and p70S6 kinase phosphorylation were increased in both the atria and ventricles of LKB1-deficient mice. Consistent with vascular endothelial growth factor mRNA and protein levels being significantly reduced in LKB1-KO mice, these mice also exhibited a reduction in capillary density of both atria and ventricles. In cultured cardiac myocytes, LKB1 silencing induced hypertrophy, which was ameliorated by the expression of a constitutively active form AMPK or by treatment with the inhibitor of mTOR, rapamycin. These findings indicate that LKB1 signaling in cardiac myocytes is essential for normal development of the atria and ventricles. Cardiac hypertrophy and dysfunction in LKB1-deficient hearts are associated with alterations in AMPK and mTOR/p70S6 kinase/eEF2 signaling and with a reduction in vascular endothelial growth factor expression and vessel rarefaction.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Animals; Antibiotics, Antineoplastic; Atrial Fibrillation; Carrier Proteins; Collagen Type I; Collagen Type II; Fibrosis; Gene Expression Regulation; Heart Atria; Hypertrophy, Left Ventricular; Mice; Mice, Knockout; Myocardium; Organ Specificity; Peptide Elongation Factor 2; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Protein Kinases; Protein Serine-Threonine Kinases; Ribosomal Protein S6 Kinases, 70-kDa; RNA, Messenger; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases

The increasing use of radiofrequency catheter ablation for the cure of atrial fibrillation has led to iatrogenic pulmonary vein stenosis as a new clinical entity. The optimal diagnostic modality and treatment for pulmonary vein stenosis and restenosis remain unclear. We report the successful treatment of pulmonary vein restenosis following percutaneous balloon angioplasty, and for the first time, following surgical bovine pericardial patch angioplasty, with endovascular stenting and adjuvant oral sirolimus. Both patients remain asymptomatic at 1 year follow-up without evidence of restenosis.

Topics: Administration, Oral; Angioplasty, Balloon; Atrial Fibrillation; Blood Vessel Prosthesis Implantation; Catheter Ablation; Echocardiography, Transesophageal; Humans; Immunosuppressive Agents; Male; Middle Aged; Pulmonary Veno-Occlusive Disease; Recurrence; Sirolimus; Stents; Ultrasonography, Doppler, Color

Aging and pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. Abnormal Ca(2+) regulation and ryanodine receptors are known to contribute to PV arrhythmogenesis.. The purpose of this study was to investigate whether aging alters PV electrophysiology, Ca(2+) regulation proteins, and responses to rapamycin, FK-506, ryanodine, and ouabain.. Conventional microelectrodes were used to record action potential and contractility in isolated PV tissue samples in 15 young (age 3 months) and 16 aged (age 3 years) rabbits before and after drug administration. Expression of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), ryanodine receptor, and Na(+)/Ca(2+) exchanger was evaluated by western blot.. Aged PVs had larger amplitude of delayed afterdepolarizations, greater depolarized resting membrane potential, longer action potential duration, and higher incidence of action potential alternans and contractile alternans with increased expression of Na(+)/Ca(2+) exchanger and ryanodine receptor and decreased expression of SERCA2a. Rapamycin (1,10,100 nM), FK-506 (0.01, 0.1, 1 microM), ryanodine (0.1, 1 microM), and ouabain (0.1, 1 microM) concentration-dependently increased PV spontaneous rates and the incidence of delayed afterdepolarizations in young and aged PVs. Compared with results in young PVs, rapamycin and FK-506 in aged PVs increased PV spontaneous rates to a greater extent and exhibited a larger delayed afterdepolarization amplitude. In PVs without spontaneous activity, rapamycin and FK-506 induced spontaneous activity only in aged PVs, but ryanodine and ouabain induced spontaneous activity in both young and aged PVs.. Aging increases PV arrhythmogenesis via abnormal Ca(2+) regulation. These findings support the concept that ryanodine receptor dysfunction may result in high PV arrhythmogenesis and aging-related arrhythmogenic vulnerability.

Topics: Age Factors; Animals; Atrial Fibrillation; Blotting, Western; Calcium; Dose-Response Relationship, Drug; Electrocardiography; Heart Atria; Microelectrodes; Myocardial Contraction; Ouabain; Pulmonary Veins; Rabbits; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Processing, Computer-Assisted; Sirolimus; Sodium-Calcium Exchanger; Tacrolimus; Tissue Culture Techniques