piperidines and Aortic-Valve-Stenosis

Objective- Calcific aortic valve disease is the most prevalent valvulopathy in Western countries. An unanticipated pathogenetic clue involving IFN (interferon) was disclosed by the finding of constitutive type I IFN activity associated with aortic valve calcification in children with the atypical Singleton-Merten syndrome. On this basis, the role of type I IFN on inflammation and calcification in human aortic valve interstitial cells (AVIC) was examined. Approach and Results- IFN-α was weakly proinflammatory but potentiated lipopolysaccharide-mediated activation of NF (nuclear factor)-κB and the ensuing induction of proinflammatory molecules in human AVIC. Stimulation with IFN-α and in combination with lipopolysaccharide promoted osteoblast-like differentiation characterized by increased osteoblastic gene expression, BMP (bone morphogenetic protein)-2 secretion, and ectopic phosphatase activity. Sex differences were observed. Likewise, IFN-α treatment of human AVICs in osteogenic medium resulted in increased formation of calcific nodules. Strikingly, IFN-α-mediated calcification was significantly higher in AVICs from males, and was blocked by tofacitinib, a JAK (Janus kinase) inhibitor, and by a BMP antagonist. A female-specific protective mechanism involving the activation of PI3K-Akt (protein kinase B) pathways and cell survival was disclosed. Females exhibited higher levels of BCL2 in valve cells and tissues and lower annexin V staining on cell stimulation. Conclusions- IFN-α acts as a proinflammatory and pro-osteogenic cytokine in AVICs, its effects being potentiated by lipopolysaccharide. Results also uncovered sex differences with lower responses in female AVICs and sex-specific mechanisms involving apoptosis. Data point to JAK/STAT (signal transducer and activator of transcription) system as a potential therapeutic target for calcific aortic valve disease.

Topics: Aortic Valve; Aortic Valve Stenosis; Apoptosis; Bone Morphogenetic Protein 2; Calcinosis; Cell Differentiation; Cells, Cultured; Cytokines; Female; Humans; Interferon Type I; Janus Kinase Inhibitors; Lipopolysaccharides; Male; NF-kappa B; Osteoblasts; Piperidines; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyrroles; Sex Factors; Signal Transduction; STAT Transcription Factors; Toll-Like Receptor 4

The authors present their own experience of the treatment of patients qualified for transcatheter aortic valve implantation (TAVI) carried out in a modern hybrid operating room. The objective of the present study was to demonstrate the initial results of conducting anaesthesia in high-risk patients qualified for the TAVI procedure (transcatheter aortic valve implantation). In addition, the authors' aim was also to point out to the special challenges of an anaesthesiologist conducting local anaesthesia in such a type of procedures and to evaluate the safety and efficacy of the TAVI procedure conducted under remifentanil analgosedation.. A retrospective analysis included patients treated during the period from September 2015, when local anaesthesia for the transcatheter aortic valve implantation was used for the first time at our centre, up to February 2016. The studied population consisted of 11 patients treated for severe aortic valve stenosis. The mean age of patients was 80 ± 7 years. Three patients were men (27%) and eight were women (73%). The study included all subsequent patients (n = 11), treated in our centre, for whom it was decided to perform TAVI under local anaesthesia.. The total hospital mortality rate was 0%. All procedures were performed in a hybrid operating room. Despite the complications observed in the described group, the hospital mortality rate during TAVI was 0%. All patients, after 12 ± 5 days of treatment, left the hospital in a good neurological condition, which was assessed based on the CPC-1 (Cerebra Performance Categories Scale) and GCS-15 (Glasgow Coma Scale) scales. With an ejection fraction of the left ventricle of 53 ± 11%, the transcatheter aortic valve was successfully implanted.. Percutaneous aortic valve implantation can be successfully conducted under remifentanil analgosedation. TAVI procedures should be performed in the conditions of a modern, well-equipped hybrid room. The aim of the anaesthesiologist should consist of conducting the least invasive anaesthesia/analgesia, bearing in mind the safety and comfort of the patient.

Topics: Aged; Aged, 80 and over; Anesthesia, Local; Anesthetics, Intravenous; Aortic Valve Stenosis; Female; Hospital Mortality; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperidines; Remifentanil; Retrospective Studies; Risk Factors; Transcatheter Aortic Valve Replacement

We report the first experience of transcatheter aortic valve implantation through a transcarotid approach under local anesthesia.. An 81-year-old gentleman with severe symptomatic aortic stenosis was referred for TAVI. He was not suitable for transfemoral, transapical, subclavian, or direct aortic approach. He had severe lung disease and was considered unsuitable for general anesthesia. We, therefore, performed the procedure under local anesthesia though the right common carotid artery (CCA) approach. Superficial cervical block was achieved with Levobupivacaine, and in addition, he also had a target controlled infusion of Remifentanil. Cerebral oximetry was monitored throughout the procedure. The CCA was accessed through surgical cut-down. Aortic valvuloplasty was performed through a 12-F sheath, and the CoreValve was deployed successfully through an 18-F sheath.. TAVI is commonly performed through femoral access under local anesthesia. The right carotid artery approach under local anesthesia requires careful monitoring of cerebral oxygen levels but allowed us to perform successful TAVI in this high risk patient when all conventional approaches were contra-indicated. Compared with a right subclavian or left carotid access, the right carotid offers more direct angle of approach allowing precise valve placement with minimal readjustment during deployment.

Topics: Aged, 80 and over; Analgesics, Opioid; Anesthesia, Local; Anesthetics, Local; Aortic Valve; Aortic Valve Stenosis; Aortography; Bupivacaine; Cardiac Catheterization; Carotid Artery, Common; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Levobupivacaine; Magnetic Resonance Angiography; Male; Nerve Block; Oximetry; Piperidines; Predictive Value of Tests; Radiography, Interventional; Remifentanil; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome

In anesthetic induction of patients with severe aortic stenosis, maintenance of normal heart rate and blood pressure is critical. Remifentanil can blunt cardiovascular responses to tracheal intubation, but may cause circulatory collapse due to potent vasodilating effect. We studied retrospectively the optimal dose of remifentanil, which blunts cardiovascular responses to tracheal intubation and provides the hemodynamic stability to patients with severe aortic stenosis.. We administerd remifentanil with three different doses (0.3 microg x kg(-1) x min(-1) : n=4, 0.5 microg x kg(-1) x min(-1): n=7, 1 microg x kg(-1) x min(-1): n=7) in anesthetic induction of patients with aortic stenosis. Systolic arterial blood pressure and heart rate before and after the tracheal intubation were recorded. The degree of change of post to pre-intubation of systolic arterial pressure and heart rate was calculated and compared among groups.. There were no significant differences in background among the groups. The ratio between before and after tracheal intubation of systolic arterial pressure was significantly lower in the group of 0.5 microg x kg(-1) x min(-1) and 1 microg x kg(-1) x min(-1). There was no significant hypotension or bradycardia which may lead to severe cardiovascular depression.. We found that more than 0.5 microg x kg(-1) x min(-1) of remifentanil can blunt cardiovascular responses to tracheal intubation without severe cardiovascular depression.

Topics: Aged; Aged, 80 and over; Anesthetics, Intravenous; Aortic Valve Stenosis; Female; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Hypnotics and Sedatives; Intubation, Intratracheal; Male; Piperidines; Remifentanil; Retrospective Studies; Severity of Illness Index

We have developed an approach where percutaneous aortic valve (PAVI) procedures are done under remifentanil-based sedation administered by an anesthetist. We report here our initial experience.. Percutaneous aortic valve implantation is proving to be an effective treatment for aortic stenosis in patients with significant comorbidity precluding surgical aortic valve replacement. Most PAVIs have been done under general anesthetic with transoesophageal echocardiography (TOE). General anesthesia in this patient group is hazardous and associated with significant complications.. CoreValve implantation was performed via the retrograde approach in 12 patients at our cardiothoracic center between December 2007 and May 2008. Three had the procedure under general anesthetic and nine under sedation. There were no differences between the groups in terms of comorbidities and clinical characteristics. The procedure was visualized using fluoroscopic aortic calcification coupled with multiple small volume aortograms. One patient converted from sedation to general anesthetic during the procedure. One patient in the general anesthetic group died from respiratory complications. There were no significant differences in procedural success, procedure time, or hospital stay between the two groups.. Percutaneous aortic valve implantation can, in the majority of cases, be performed under remifentanil-based sedation. Our initial experience suggests that this should result in a shorter implant procedure time, reduced stay in high dependency areas, and shorter time to hospital discharge.

Topics: Aged; Aged, 80 and over; Anesthesia, General; Aortic Valve; Aortic Valve Stenosis; Catheterization; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Hypnotics and Sedatives; Length of Stay; Male; Piperidines; Prosthesis Design; Remifentanil; Time Factors; Treatment Outcome

Although heart disease is now the joint leading cause of maternal mortality in the UK, critical aortic stenosis is rarely encountered in parturients. Caesarean section is advisable in these patients to minimise the haemodynamic stress of labour and delivery. The use of an opioid-based general anaesthetic technique also helps to maintain cardiovascular stability. During a two-year period, four women with critical aortic stenosis requiring caesarean section presented to our institution. In all women, a rapid sequence induction of anaesthesia was performed using etomidate 0.1 to 0.2 mg.kg(-1), suxamethonium 1.5 mg.kg(-1) and remifentanil 2 to 4 micrograms.kg(-1). Anaesthesia was then maintained with isoflurane, nitrous oxide and a remifentanil infusion at 0.05 to 0.15 micrograms.kg(-1)min(-1). There was good haemodynamic stability throughout, except for a short period in one patient who became hypotensive after a significant post-partum haemorrhage secondary to uterine atony. All parturients were successfully extubated at the end of surgery and made excellent postoperative recoveries. Neonates were born in good condition with Apgar scores of 10, 9, 6 and 5 at 1 min and 10, 10, 10 and 10 at 5 min. We suggest that remifentanil is an ideal agent for parturients with severe aortic stenosis requiring general anaesthesia for caesarean section. Remifentanil provides cardiovascular stability in conjunction with rapid emergence from anaesthesia in the parturient and minimal side effects in the neonate.

Topics: Adult; Anesthesia, General; Anesthesia, Intravenous; Anesthesia, Obstetrical; Anesthetics, Intravenous; Aortic Valve Stenosis; Apgar Score; Cesarean Section; Echocardiography; Female; Hemodynamics; Humans; Infant, Newborn; Male; Monitoring, Intraoperative; Piperidines; Pregnancy; Pregnancy Complications, Cardiovascular; Remifentanil

After an initial pilot study in five patients, the effect of flecainide on chronic ventricular arrhythmias was tested during 48-hour oral administration of 250 mg twice a day in nine further patients with previously drug-resistant chronic, stable ventricular arrhythmias. Mean age was 45.9 +/- 14.9 years; seven patients were male. Three patients had coronary artery disease, whereas the diagnoses in the remaining patients were congestive cardiomyopathy, aortic stenosis or no apparent heart disease. Continuous Holter monitoring with quantitative evaluation was performed in all patients for 24 hours before and during a two days' period of treatment. The mean number of ventricular ectopic beats decreased from 20.3 +/- 6.4 beats/min during hour six of treatment and further to 3.1 +/- 7.7 beats/min during hour 25 to 48 after onset of treatment. In either of nine patients, the mean decrease in ventricular ectopic rate was 97.5%. In only one patient, therapy was ineffective, Ventricular couplets were completely suppressed in six of eight cases. Looking at the spontaneous variability of ventricular ectopic beats during the control period, eight of nine patients showed a decrease which considerably exceeded the statistically necessary one. Headache of moderate degree was reported in one case in the pilot study. Therapy had to be stopped after the first dose because of QRS widening in another patient. In conclusion, this short-term study suggests that flecainide may be an effective drug for the management of ventricular arrhythmias.

Topics: Adult; Anti-Arrhythmia Agents; Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Chronic Disease; Coronary Disease; Electrocardiography; Female; Flecainide; Heart Ventricles; Humans; Male; Middle Aged; Piperidines