Left atrial appendage occlusion in patients suffering from advanced chronic kidney disease (stage 4 and 5). Long-term follow-up.

INTRODUCTION AND OBJECTIVES: Advanced chronic kidney disease (A-CKD) combined with atrial fibrillation increases the risk of both thrombogenic and bleeding events. Left atrial appendage occlusion (LAAO) may be an alternative to oral anticoagulation to prevent thromboembolic events. We aimed to evaluate the outcomes of LAAO in patients with A-CKD. METHODS: Comparison at long-term follow-up of patients diagnosed with and without A-CKD (eGFR<30 mL/min/1.73 m2 ) who underwent LAAO between 2009 and May 2022. RESULTS: Five hundred seventy-three patients were included. Eighty-one (14%) were diagnosed with A-CKD. There were no differences in sex, age, and cardiovascular risk factors, except for diabetes which was more frequent in patients with A-CKD. The control group had higher rates of stroke, both ischemic and hemorrhagic. There were no differences in the CHA2 DS2 -VASc score, although A-CKD patients had a higher bleeding risk according to the HASBLED scale. Global procedural success was 99.1%. At follow-up, there were no differences in stroke rate: at 1-year (HR: 1.22, IC-95%: 0.14-10.42, p = 0.861); at 5-years (HR: 0.60, IC-95%: 0.08-4.58, p = 0.594). Although bleeding events were higher in the A-CKD group, no differences were found in major bleeding (defined BARC ≥ 3) at 1-year (HR: 1.34, IC-95%: 0.63-2.88, p = 0.464) or at 5-years follow-up (HR: 1.30, IC-95%: 0.69-2.48, p = 0.434). Mortality rate at 5 years was higher in the A-CKD patients (HR: 1.84, IC-95%: 1.18-2.87, p = 0.012). CONCLUSIONS: LAAO is an effective and safe treatment in A-CKD patients to prevent ischemic events and bleeding. This strategy could be an alternative to oral anticoagulation in this high-risk group of patients.

Complex Left Atrial Appendage Occlusion Using the Novel Amplatzer Steerable Delivery Sheath.

Left atrial appendage (LAA) occlusion has emerged as an al- ternative to oral anticoagulation in non-valvular atrial fibril- lation. The success rate is high, but we are still facing some challenging LAA anatomies that may increase the risk of sub- optimal results. These images show that the Amplatzer steer- able sheath is useful for LAA occlusion, especially in cases with challenging anatomies. Small variations of the distal end angle can improve the success rate and reduce complications.

Percutaneous Closure of Mitral Paravalvular Leak: Long-Term Results in a Single-Center Experience.

BACKGROUND: Paravalvular leak occurs in 5-17% of patients following surgical valve replacement, more often in mitral position. The prognosis without treatment is poor. Percutaneous device closure represents an alternative to repeat surgery. The objective of this work is to evaluate the medium and long-term results in the percutaneous closure of PVL in mitral prosthesis. METHODS: This observational study is based on a retrospective registry including consecutive mitral PVL cases undergoing percutaneous closure at a single tertiary-care center from April 2010 to December 2020. The safety and efficacy results of the procedure, at 90 days and in the long term, were analyzed. Also, predictors of procedure failure and long-term events were identified. RESULTS: A total of 128 consecutive mitral paravalvular leak closure procedures were included. Technical success was achieved in 115 (89.8%) procedures. The presence of multiple PVLs was the sole factor that independently predicted procedural failure. Median follow-up of our sample was 41.8 months (mean 47.7 ± 35.7 months). Underlying hemolytic anemia as the indication for PVL closure, a recent admission for decompensated HF, and lack of improvement in functional class emerged as consistent predictors of MACE and death during long-term follow-up, while lack of procedural success during the first PVL procedure and chronic kidney disease were also associated with MACE during follow-up. CONCLUSIONS: Percutaneous mitral PVL closure displayed high technical and procedural success rates, with an acceptable safety profile, in a high-risk population. Percutaneous mitral PVL closure achieved an improvement in short- and long-term functional class and a reduction of hemolysis in the vast majority of patients. In addition, long-term survival in our study was good, in particular for patients undergoing successful PVL closure procedures.

Efficacy and safety of percutaneous patent foramen ovale closure in patients with a hypercoagulable disorder.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke reduces the rate of recurrent events. Although presence of thrombophilia increases the risk for paradoxical emboli through a PFO, such patients were excluded from large randomized trials. OBJECTIVES: We compared the safety and efficacy of percutaneous PFO closure in patients with and without a hypercoagulable state. METHODS: Data from 800 consecutive patients undergoing percutaneous PFO closure in our medical center were analyzed. All patients were independently evaluated by specialists in neurology, cardiology, hematology, and vascular medicine. A post-procedural treatment of at least 3 months of anticoagulation was utilized in patients with thrombophilia. Follow-up events included death, recurrent neurological events, and the need for reintervention for significant residual shunt. RESULTS: A hypercoagulable state was found in 239 patients (29.9%). At median follow-up of 41.9 months, there were no differences in the frequencies of stroke or transient ischemic attack between patients with or without thrombophilia (2.5% in non-hypercoagulable group vs. 3.4% in hypercoagulable group, log-rank test p = 0.35). There were no significant differences in baseline demographics, echocardiographic characteristics, procedural success, or complications between groups. CONCLUSION: Percutaneous PFO closure is a safe and effective therapeutic approach for patients with cryptogenic stroke and an underlying hypercoagulable state.

Two-year clinical outcome from the Iberian registry patients after left atrial appendage closure.

AIMS: The aim of this study was to observe the percentage of thromboembolic and haemorrhagic events over a 2-year follow-up in patients with non-valvular atrial fibrillation (NVAF) undergoing closure of the left atrial appendage (LAA) with an occlusion device. Observed events and CHADS2 (congestive heart failure, hypertension, age, diabetes, stroke history), CHA2DS2-VASc (also adding: vascular disease and sex) and HAS-BLED (hypertension, abnormal liver/renal function, stroke history, bleeding predisposition, labile international normalised ratios, elderly, drugs/alcohol use)-predicted events were compared. METHODS: LAA closure with an occlusion device was performed in 167 NVAF patients contraindicated for oral anticoagulants and recruited from 12 hospitals between 2009 and 2013. At least two transoesophageal echocardiograms were performed in the first 6 months postimplantation. Antithrombotics included clopidogrel and aspirin. Patients were monitored for death, stroke, major and relevant bleeding and hospitalisation for concomitant conditions. Mean age was 74.68±8.58, median follow-up was 24 months, 5.38% had intraoperative complications and implantation was successful in 94.6% of subjects. Mortality during follow-up was 10.8%, mostly (9.5%) non-cardiac related. Bleeding occurred in 10.1% of subjects, 5.7% major and 4.4% minor though relevant, and 4.4% suffered stroke. Major bleeding and stroke/transient ischaemic attack events within 2 years (annual event rates, 290 patients/year) were less frequent than expected from CHADS2 (2.4% vs 9.6%), CHA2DS2-VASc (2.4% vs 8.3%) and HAS-BLED (3.1% vs 6.6%) risk scores (p<0.001, p=0.003, p=0.047, respectively). CONCLUSIONS: LAA closure with an occlusion device in patients contraindicated for oral anticoagulants is a therapeutic option associated with fewer thromboembolic and haemorrhagic events than expected from risk scores, particularly in the second year postimplantation.

Optical coherence tomography: its value in intravascular diagnosis today.

Optical coherence tomography is a recently developed high-resolution intravascular diagnostic technique. Initially, it was mainly used for characterizing atherosclerotic plaque because it served a number of functions, from identifying plaque with high lipid content to detecting macrophage accumulation, both of which are associated with plaque instability. Currently, there is growing interest in the value of optical coherence tomography in the area of coronary intervention, where the technique offers significant advantages over more widespread intravascular diagnostic techniques such as intravascular ultrasound: its higher resolution means that the vessel lumen diameter can be measured more precisely, periprocedural complications such microdissection of the coronary artery can be detected, stent apposition relative to the vessel wall can be optimized, neointimal hyperplasia can be detected after stent implantation, and neointimal thickness can be measured. It would therefore appear to be a very useful technique for interventional cardiologists. This review article considers the technical details of the technique and its applications, and compares it with other intravascular diagnostic techniques.

Tomografía de coherencia óptica: situación actual en el diagnóstico intravascular / Optical coherence tomography: its value in intravascular diagnosis today

La tomografía de coherencia óptica es una técnica de diagnóstico intravascular de alta resolución de reciente desarrollo. Inicialmente se centró en la caracterización de la placa arteriosclerótica, ya que permite desde la identificación de placas con alto contenido lipídico hasta la acumulación de macrófagos, ambos hechos relacionados con la inestabilidad de la placa. Actualmente ha cobrado un creciente interés su utilidad en el campo del intervencionismo coronario; presenta grandes ventajas sobre otras técnicas de diagnóstico endovascular más extendidas como la ecografía intravascular: el diámetro de la luz del vaso puede medirse de forma más exacta gracias a su mayor resolución, permite detectar complicaciones del procedimiento como la microdisección de la arteria, puede poner de manifiesto la correcta aposición del stent a la pared del vaso, permite detectar la hiperplasia neointimal tras el implante del stent y la medición del espesor de la neoíntima. Por lo tanto, parece ser una herramienta de gran utilidad para el cardiólogo intervencionista. En esta revisión se analizan los aspectos técnicos y las aplicaciones de esta técnica y se la compara con otras técnicas de diagnóstico intravascular (AU)

Optical coherence tomography is a recently developed high-resolution intravascular diagnostic technique. Initially, it was mainly used for characterizing atherosclerotic plaque because it served a number of functions, from identifying plaque with high lipid content to detecting macrophage accumulation, both of which are associated with plaque instability. Currently, there is growing interest in the value of optical coherence tomography in the area of coronary intervention, where the technique offers significant advantages over more widespread intravascular diagnostic techniques such as intravascular ultrasound: its higher resolution means that the vessel lumen diameter can be measured more precisely, periprocedural complications such microdissection of the coronary artery can be detected, stent apposition relative to the vessel wall can be optimized, neointimal hyperplasia can be detected after stent implantation, and neointimal thickness can be measured. It would therefore appear to be a very useful technique for interventional cardiologists. This review article considers the technical details of the technique and its applications, and compares it with other intravascular diagnostic techniques (AU)

Comparison of procedural and in-hospital outcomes of percutaneous balloon aortic valvuloplasty in patients >80 years versus patients < or =80 years.

Percutaneous balloon aortic valvuloplasty (PBAV) is a procedure used for palliation, bridging to surgery, and as an integral step in the procedure for percutaneous aortic valve replacement. Older patients with severe aortic stenosis are thought to have greater risk for adverse perioperative events than younger patients. The aim of this study was to evaluate the outcomes of patients aged >80 years and those aged < or =80 years who underwent PBAV to identify factors associated with adverse clinical outcomes. This was a retrospective study of 111 consecutive patients with severe symptomatic aortic stenosis who underwent retrograde PBAV at Massachusetts General Hospital from December 2004 to December 2008. Forty-nine patients (44%) were men, and the mean age for the whole group was 82 +/- 8 years. Patients were divided into 2 age groups: those aged >80 years (n = 73) and those aged < or =80 years (n = 38). Procedural outcomes, complications, and in-hospital adverse events were compared. Multivariate logistic regression was used for the adjusted analysis. Nearly 90% of patients were in New York Heart Association class III or IV. Patients aged >80 years had lower baseline ejection fractions (43.5% vs 56.1%, p <0.01) and smaller aortic valve areas (0.59 vs 0.73 cm(2), p <0.01). Although the 2 age groups had a similar percentage of aortic valve area increase (55.5% vs 45.2%, p = 0.28), those aged >80 years had smaller post-PBAV aortic valve areas (0.89 vs 1.02 cm(2), p <0.05). Overall, in-hospital mortality was 8.1%, with no significant differences between the groups. Advanced age was not an independent predictor of in-hospital death, myocardial infarction, stroke, cardiac arrest, or tamponade; however, patients aged >80 years had a significantly higher incidence of intraprocedural emergent intubation and cardiopulmonary resuscitation compared to the younger group. New York Heart Association class was the only independent predictor of worse in-hospital outcomes. In conclusion, compared to younger patients, those aged >80 years had less favorable preprocedural characteristics for PBAV but similar overall in-hospital clinical outcomes. Patients aged >80 years had significantly higher incidence of emergent intubation and cardiopulmonary resuscitation during PBAV.

Surgical results and complications in a series of 71 consecutive cervical spondylotic corpectomies.

BACKGROUND: Cervical corpectomy is a common procedure in spondylosis. It is normally a well-tolerated surgery and clinical improvement is widely described. However, it is associated with potential risky complications (subsidence, clinical deterioration, vertebral artery injury...); thus, a judicious surgical indication and a good technique are required. METHODS: We revised retrospectively the clinical evolution and complications of 71 spondylotic corpectomies in a series of 100 consecutive patients operated on due to different ethiological causes from January 2001 to September 2007 at our hospital. RESULTS: Among the 71 cases, a single-level corpectomy was performed in 46 cases and a two level in 25. The graft we used was a titanium mesh filled with bone from the removed vertebra in 69 cases and a telescopic cage in two additional cases. We stabilized the construction with a locking plate. The presurgical clinical status of patients, according to the Nurick grading scale was as follows: 30 patients were grade 0, 12 were grade 1, eight were grade 2, 14 were grade 3, five were grade 4 and two were grade 5. After decompression, 41 patients were considered cured, three were grade 1, seven were grade 2, 11 were grade 3, seven were grade 4 and one was grade 5. One patient died in the postoperative period. Globally, 44 (62%) patients achieved good or excellent results (grades 0-1), 15 (21%) remained as previously (grade >1), six (8%) improved partially and five (7%) worsened. Forty (95%) grades 0 and 1 patients became cured, and four (50%), four (31%) and two (28%) grades 2, 3 and 4-5, respectively, experienced a postsurgical improvement. Significant complications occurred in 18 (25%) patients. The most significant were: hardware failure (n = 7), subsidence in five cases (one required intervention) and incorrect screw placement in two (one required intervention); permanent dysphagia (n = 4) and dysphonia (n = 1); postsurgical neurological worsening in three cases (two improved and one remained grade 4); vertebral artery injury in one case; and an urgent evacuation of a prevertebral hematoma. One patient died due to respiratory disturbances. CONCLUSIONS: Cervical corpectomy is efficient for spinal cord decompression, especially when anterior components (disk osteophyte, OPLL...) bulge in the spinal cord. A three or more level corpectomy was not considered in this series since they may be associated to high rate morbidity. We found that this decompression led to better clinical results in patient grades 0 and 1 and to poorer results as myelopathy progressed. Among complications, subsidence was the most frequent specific one, but since it was rarely associated with symptoms, the majority of patients were successfully treated conservatively.

Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas.

Gliomas are the most important group of malignant primary brain tumors and one of the most aggressive forms of cancer. During the last years, several studies have demonstrated that cannabinoids induce apoptosis of glioma cells and inhibit angiogenesis of gliomas in vivo. As the effects of cannabinoids rely on CB(1) and CB(2) receptors activation, the aim of the present study was to investigate both receptors protein expression in cellular membrane homogenates of human glial tumors using specific antibodies raised against these proteins. Additionally, we studied the functionality of the cannabinoid receptors in glioblastomas by using WIN 55,212-2 stimulated [(35)S]GTPgammaS binding. Western blot analysis showed that CB(1) receptor immunoreactivity was significantly lower in glioblastoma multiforme (-43%, n=10; p<0.05) than in normal post-mortem brain tissue (n=16). No significant differences were found for astrocytoma (n=6) and meningioma (n=8) samples. Conversely, CB(2) receptor immunoreactivity was significantly greater in membranes of glioblastoma multiforme (765%, n=9; p<0.05) and astrocytoma (471%, n=4; p<0.05) than in control brain tissue (n=10). Finally, the maximal stimulation of [(35)S]GTPgammaS binding by WIN 55,212-2 was significantly lower in glioblastomas (134+/-4%) than in control membranes (183+/-2%; p<0.05). The basal [(35)S]GTPgammaS binding and the EC(50) values were not significantly different between both groups. The present results demonstrate opposite changes in CB(1) and CB(2) receptor protein expression in human gliomas. These changes may be of interest for further research about the therapeutic effects of cannabinoids in glial tumors.

Impact of rapid ventricular pacing during percutaneous balloon aortic valvuloplasty in patients with critical aortic stenosis: should we be using it?

BACKGROUND: Rapid ventricular pacing (RP) during percutaneous balloon aortic valvuloplasty (BAV) facilitates balloon positioning by preventing the "watermelon seeding" effect during balloon inflation. The clinical consequences of RP BAV have never been compared with standard BAV in which rapid pacing in not used. We evaluated the immediate results and in-hospital adverse events of patients with severe aortic stenosis (AS) undergoing BAV with and without RP. METHODS: This is a retrospective study of patients with severe AS undergoing retrograde BAV. Patients who underwent BAV with RP were compared to those who did not receive RP during BAV. Procedural outcomes, complications, and in-hospital adverse events were compared between both groups. Stratified analyses were performed to evaluate RP in pre-specified subsets for confounding and effect modification. RESULTS: Between January 2005 and December 2008, 111 consecutive patients underwent retrograde BAV at Massachusetts General Hospital. Sixty-seven patients underwent BAV with RP. Nearly 90% of patients were NYHA class III or IV and the mean AVA was 0.64 cm(2). Baseline characteristics and balloon sizes were similar in the two groups. The average post-BAV AVA was smaller in the RP group compared to the no-RP group (0.87 v. 1.02 cm(2), p = 0.02). Pre and post-cardiac output, in-hospital mortality, myocardial infarction, stroke, frequency of cardiopulmonary arrest, vasopressor use, and major complications were similar in the two groups. CONCLUSIONS: 1) RP allows precise balloon placement during BAV. 2) RP BAV is associated with lower post-BAV AVA. 3) RP BAV may be safely performed in patients with high-risk cardiac features.

DNA copy number variation and gene expression analyses reveal the implication of specific oncogenes and genes in GBM.

To understand the pathogenesis of glioblastoma multiforme (GBM) we used high-resolution comparative genomic hybridization arrays and gene expression microarrays to identify DNA copy number alterations and gene expression changes in comparable sets of GBM samples. Gains were detected at chromosomes 1, 2, 7, 9, 12, 19, and 20 and losses at 6, 9, and 10. Gene expression analyses identified specific genes overexpressed in GBM mapping at amplified chromosomal regions. Among these genes we found genes involved in angiogenesis, extracellular matrix remodeling and several oncogenes. DNA copy number analysis along with gene expression profiles provides a powerful strategy to understand tumor progression and identification of genes involved in GBM pathogenesis.

Outcome of bilateral deep brain subthalamic stimulation in patients carrying the R1441G mutation in the LRRK2 dardarin gene.

OBJECTIVE: Deep brain subthalamic stimulation provides symptomatic relief to patients with Parkinson's disease. The present study analyzes the postoperative outcome of deep brain subthalamic stimulation in patients carrying the R1441G mutation in the leucine-rich repeat kinase-2 (LRRK2) (dardarin) gene. METHODS: Five of the 48 patients treated in our unit carried a mutation in the LRRK2 (dardarin) gene. All five met the Core Assessment Program for Surgical Interventional Therapies criteria for inclusion in the surgical program. Pre- and postoperative assessment (6 mo) was made using the Unified Parkinson Disease Rating Scale II, Unified Parkinson Disease Rating Scale III, and Parkinson's Disease Questionnaire-39 scores, as well as the type and dosage of drugs used. RESULTS: The response to L-dopa after 6 months was similar to the baseline in all four patients. One suffered a stroke four months after surgery and is not eligible for evaluation. The improvements in motor response, daily life activities, and quality of life were limited (18, 22, and 33%, respectively) and were lower than those of the control group (39, 45, and 41%, respectively). DISCUSSION: Carriers of the R1441G mutation were clinically analogous to the rest of similarly operated patients with idiopathic Parkinson's disease. However, the response to deep brain subthalamic stimulation was worse among the former. The explanation for this negative result is unclear because all patients maintained an excellent response to L-dopa. Further larger studies are needed to confirm these findings.

Monoamine oxidase B activity is increased in human gliomas.

Glial tumours are the most common type of brain neoplasm in humans. Tumour classification and grading represent key factors for patient management. However, current grading schemes are still limited by subjective histological criteria. In this context, gliosis has been linked to increases in monoamine oxidase B (MAO-B) activity. Thus, in the present study, MAO-B activity in membranes of glial tumours (n=20), meningiomas (n=12) and non-pathological human brains (n=15) was quantified by [14C]PEA oxidation. MAO-B activity was significantly greater in glioblastoma multiformes than in postmortem control brains (p<0.01) or meningiomas (p<0.001). There were no significant differences in MAO-B activity between glioblastoma multiformes (n=11) and low-grade astrocytomas (n=3) or anaplastic astrocytomas (n=6). In conclusion, the present results demonstrate a significant and selective increase in MAO-B activity in human gliomas when compared with meningiomas or non-tumoural tissue. These results suggest that the quantification of MAO-B activity may be a useful diagnostic tool for differentiating glial tumours from other types of brain tumours or surrounding normal brain tissue.

Electrophysiological characterization of substantia nigra dopaminergic neurons in partially lesioned rats: effects of subthalamotomy and levodopa treatment.

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the main histopathological characteristic of Parkinson's disease. We studied the electrophysiological characteristics of the spontaneous activity of substantia nigra pars compacta dopaminergic neurons in rats with a partial, unilateral, 6-hydroxydopamine lesion of the nigrostriatal pathway. In addition, the effects of subthalamotomy and prolonged levodopa treatment on the activity of dopaminergic neurons were investigated. As a result of the lesion ( approximately 50% neuronal loss), the number of spontaneously active neurons was significantly reduced. Basal firing rate, burst firing and responsiveness to intravenously administered apomorphine remained unchanged. In contrast, the variation coefficient, a measure of interspike interval regularity, was significantly increased. Ibotenic acid (10 microg) lesion of the ipsilateral subthalamic nucleus in lesioned rats did not modify the electrophysiological parameters. However, prolonged levodopa treatment (100 mg/kg/day + benserazide 25 mg/kg/day, 14 days) reversed the irregularity observed in cells from lesioned rats, while it induced an irregular firing pattern in cells from intact rats. Our results using an experimental model of moderate Parkinson's disease indicate that surviving substantia nigra pars compacta dopaminergic neurons fire irregularly. In this model, subthalamotomy does not modify the firing pattern while levodopa treatment efficiently restores normal firing of SNpc neurons and does not appear to be toxic to them.

Parkinson's disease-like presentation of multiple system atrophy with poor response to STN stimulation: a clinicopathological case report.

We report on a clinicopathological case of multiple system atrophy with good response to levodopa and subsequent development of motor complications. Because the subject complied with all the inclusion criteria (Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease), bilateral subthalamic nucleus deep brain stimulation electrodes were implanted.