Personalized pulmonary vein isolation with very high-power short-duration lesions guided by left atrial wall thickness: the QDOT-by-LAWT randomized trial.

AIMS: Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using very high-power short-duration (vHPSD) radiofrequency (RF) ablation proved to be safe and effective. However, vHPSD applications result in shallower lesions that might not be always transmural. Multidetector computed tomography-derived left atrial wall thickness (LAWT) maps could enable a thickness-guided switching from vHPSD to the standard-power ablation mode. The aim of this randomized trial was to compare the safety, the efficacy, and the efficiency of a LAWT-guided vHPSD PVI approach with those of the CLOSE protocol for PAF ablation (NCT04298177). METHODS AND RESULTS: Consecutive patients referred for first-time PAF ablation were randomized on a 1:1 basis. In the QDOT-by-LAWT arm, for LAWT ≤2.5 mm, vHPSD ablation was performed; for points with LAWT > 2.5 mm, standard-power RF ablation titrating ablation index (AI) according to the local LAWT was performed. In the CLOSE arm, LAWT information was not available to the operator; ablation was performed according to the CLOSE study settings: AI ≥400 at the posterior wall and ≥550 at the anterior wall. A total of 162 patients were included. In the QDOT-by-LAWT group, a significant reduction in procedure time (40 vs. 70 min; P < 0.001) and RF time (6.6 vs. 25.7 min; P < 0.001) was observed. No difference was observed between the groups regarding complication rate (P = 0.99) and first-pass isolation (P = 0.99). At 12-month follow-up, no significant differences occurred in atrial arrhythmia-free survival between groups (P = 0.88). CONCLUSION: LAWT-guided PVI combining vHPSD and standard-power ablation is not inferior to the CLOSE protocol in terms of 1-year atrial arrhythmia-free survival and demonstrated a reduction in procedural and RF times.

Iatrogenic Shapiro syndrome: a case report.

OBJECTIVES: Shapiro's syndrome (SS) is a rare condition characterized by spontaneous periodic hypothermia. The underlying pathophysiological mechanisms and etiology of this syndrome remain controversial, and fewer than 100 cases have been reported to date. The objective of this case report is to present a unique iatrogenic case of SS and contribute additional insights into the underlying etiology of this rare disorder. METHODS: We conducted an analysis of existing medical literature and described a clinical case of SS secondary to a neurosurgical procedure. RESULTS: To our knowledge, we present the first iatrogenic case of SS in a 53-year-old woman who underwent a partial right parieto-occipital lobectomy in 2003 as a treatment for refractory epilepsy. Several years after the surgical procedure, she began experiencing recurrent episodes of hypothermia. Brain magnetic resonance imaging (MRI) revealed the absence of the splenium of the corpus callosum (CC) and pituitary hyperplasia. After ruling out other potential causes of hypothermia, a diagnosis of SS was made. DISCUSSION: The most plausible mechanism to explain the recurrent hypothermia associated with SS in our patient is a probable disruption of the pathways involved in thermoregulation through the CC as a consequence of the surgical procedure. This case report provides further insights into the etiology of this rare disorder.

Personalized pulmonary vein antrum isolation guided by left atrial wall thickness for persistent atrial fibrillation.

AIMS: Pulmonary vein (PV) antrum isolation proved to be effective for treating persistent atrial fibrillation (PeAF). We sought to investigate the results of a personalized approach aimed at adapting the ablation index (AI) to the local left atrial wall thickness (LAWT) in a cohort of consecutive patients with PeAF. METHODS AND RESULTS: Consecutive patients referred for PeAF first ablation were prospectively enrolled. The LAWT three-dimensional maps were obtained from pre-procedure multidetector computed tomography and integrated into the navigation system. Ablation index was titrated according to the local LAWT, and the ablation line was personalized to avoid the thickest regions while encircling the PV antrum. A total of 121 patients (69.4% male, age 64.5 ± 9.5 years) were included. Procedure time was 57 min (IQR 50-67), fluoroscopy time was 43 s (IQR 20-71), and radiofrequency (RF) time was 16.5 min (IQR 14.3-18.4). The median AI tailored to the local LAWT was 387 (IQR 360-410) for the anterior wall and 335 (IQR 300-375) for the posterior wall. First-pass PV antrum isolation was obtained in 103 (85%) of the right PVs and 103 (85%) of the left PVs. Median LAWT values were higher for PVs without first-pass isolation as compared to the whole cohort (P = 0.02 for left PVs and P = 0.03 for right PVs). Recurrence-free survival was 79% at 12 month follow-up. CONCLUSION: In this prospective study, LAWT-guided PV antrum isolation for PeAF was effective and efficient, requiring low procedure, fluoroscopy, and RF time. A randomized trial comparing the LAWT-guided ablation with the standard of practice is in progress (ClinicalTrials.gov, NCT05396534).

Preventive substrate ablation in chronic post-myocardial infarction patients with high-risk scar characteristics for ventricular arrhythmias: rationale and design of PREVENT-VT study.

BACKGROUND: Recent studies showed that an early strategy for ventricular tachycardia (VT) ablation resulted in reduction of VT episodes or mortality. Cardiac magnetic resonance (CMR)-derived border zone channel (BZC) mass has proved to be a strong non-invasive predictor of VT in post-myocardial infarction (MI). CMR-guided VT substrate ablation proved to be safe and effective for reducing sudden cardiac death (SCD) and VA occurrence. METHODS: PREVENT-VT is a prospective, randomized, multicenter, and controlled trial designed to evaluate the safety and efficacy of prophylactic CMR-guided VT substrate ablation in chronic post-MI patients with CMR-derived arrhythmogenic scar characteristics. Chronic post-MI patients with late gadolinium enhancement (LGE) CMR will be evaluated. CMR images will be post-processed and the BZC mass measured: patients with a BZC mass > 5.15 g will be eligible. Consecutive patients will be enrolled at 3 centers and randomized on a 1:1 basis to undergo a VT substrate ablation (ABLATE arm) or optimal medical treatment (OMT arm). Primary prevention ICD will be implanted following guideline recommendations, while non-ICD candidates will be implanted with an implantable cardiac monitor (ICM). The primary endpoint is a composite outcome of sudden cardiac death (SCD) or sustained monomorphic VT, either treated by an ICD or documented with ICM. Secondary endpoints are procedural safety and efficiency outcomes of CMR-guided ablation. DISCUSSION: In some patients, the first VA episode causes SCD or severe neurological damage. The aim of the PREVENT-VT is to evaluate whether primary preventive substrate ablation may be a safe and effective prophylactic therapy for reducing SCD and VA occurrence in patients with previous MI and high-risk scar characteristics based on CMR. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04675073, registered on January 1, 2021.

Use of virtual reality for procedural planning of transcatheter aortic valve replacement.

This study sought to evaluate the impact of virtual reality (VR) tools in procedural planning of transcatheter aortic valve replacement. A prospective study involving 11 patients referred for transcatheter aortic valve replacement was conducted. A multidetector computed tomography was used to acquire and segment the anatomy of the access route and landing zone. From the information obtained with the multidetector computed tomography in DICOM format, we built a virtual platform (VisuaMed, Techer Team, Valencia, Spain) that contains all the clinical information of the patients and a virtualized model of their anatomy. Wearing VR devices, the professional was able to 'walk inside' the anatomy in an interactive and immersive way. Decisions after the evaluation of routine clinical images were compared with those after experience with VR models and intraprocedural findings.

Relationship between the posterior atrial wall and the esophagus: Esophageal position during atrial fibrillation ablation.

Background: Atrial fibrillation ablation implies a risk of esophageal thermal injury. Esophageal position can be analyzed with imaging techniques, but evidence for esophageal mobility is inconsistent. Objectives: The purpose of this study was to analyze esophageal position stability from one procedure to another and during a single procedure. Methods: Esophageal position was compared in 2 patient groups. First, preprocedural multidetector computerized tomography (MDCT) of first pulmonary vein isolation and redo intervention (redo group) was segmented with ADAS 3D™ to compare the stability of the atrioesophageal isodistance prints. Second, 3 imaging modalities were compared for the same procedure (multimodality group): (1) preprocedural MDCT; (2) intraprocedural fluoroscopy obtained with the transesophageal echocardiographic probe in place with CARTOUNIVU™; and (3) esophageal fast anatomic map (FAM) at the end of the procedure. Esophageal position correlation between different imaging techniques was computed in MATLAB using semiautomatic segmentation analysis. Results: Thirty-five redo patients were analyzed and showed a mean atrioesophageal distance of 1.2 ± 0.6 mm and a correlation between first and redo procedure esophageal fingerprint of 91% ± 5%. Only 3 patients (8%) had a clearly different position. The multi-imaging group was composed of 100 patients. Esophageal position correlation between MDCT and CARTOUNIVU was 82% ± 10%; between MDCT and esophageal FAM was 80% ± 12%; and between esophageal FAM and CARTOUNIVU was 83% ± 15%. Conclusion: There is high stability of esophageal position between procedures and from the beginning to the end of a procedure. Further research is undergoing to test the clinical utility of the esophageal fingerprinted isodistance map to the posterior atrial wall.

Unraveling Bicuspid Aortic Valve Enigmas by Multimodality Imaging: Clinical Implications.

Multimodality imaging is the basis of the diagnosis, follow-up, and surgical management of bicuspid aortic valve (BAV) patients. Transthoracic echocardiography (TTE) is used in our clinical routine practice as a first line imaging for BAV diagnosis, valvular phenotyping and function, measurement of thoracic aorta, exclusion of other aortic malformations, and for the assessment of complications such are infective endocarditis and aortic. Nevertheless, TTE is less useful if we want to assess accurately other aortic segments such as mid-distal ascending aorta, where computed tomography (CT) and magnetic resonance (CMR) could improve the precision of aorta size measurement by multiplanar reconstructions. A major advantage of CT is its superior spatial resolution, which affords a better definition of valve morphology and calcification, accuracy, and reproducibility of ascending aorta size, and allows for coronary artery assessment. Moreover, CMR offers the opportunity of being able to evaluate aortic functional properties and blood flow patterns. In this setting, new developed sequences such as 4D-flow may provide new parameters to predict events during follow up. The integration of all multimodality information facilitates a comprehensive evaluation of morphologic and dynamic features, stratification of the risk, and therapy guidance of this cohort of patients.

Personalized paroxysmal atrial fibrillation ablation by tailoring ablation index to the left atrial wall thickness: the 'Ablate by-LAW' single-centre study-a pilot study.

AIMS: To determine if adapting the ablation index (AI) to the left atrial wall thickness (LAWT), which is a determinant of lesion transmurality, is feasible, effective, and safe during paroxysmal atrial fibrillation (PAF) ablation. METHODS AND RESULTS: Consecutive patients referred for PAF first ablation. Left atrial wall thickness three-dimensional maps were obtained from multidetector computed tomography and integrated into the CARTO navigation system. Left atrial wall thickness was categorized into 1 mm layers and AI was titrated to the LAWT. The ablation line was personalized to avoid thicker regions. Primary endpoints were acute efficacy and safety, and freedom from atrial fibrillation (AF) recurrences. Follow-up (FU) was scheduled at 1, 3, 6, and every 6 months thereafter. Ninety patients [60 (67%) male, age 58 ± 13 years] were included. Mean LAWT was 1.25 ± 0.62 mm. Mean AI was 366 ± 26 on the right pulmonary veins with a first-pass isolation in 84 (93%) patients and 380 ± 42 on the left pulmonary veins with first-pass in 87 (97%). Procedure time was 59 min (49-66); radiofrequency (RF) time 14 min (12.5-16); and fluoroscopy time 0.7 min (0.5-1.4). No major complication occurred. Eighty-four out of 90 (93.3%) patients were free of recurrence after a mean FU of 16 ± 4 months. CONCLUSION: Personalized AF ablation, adapting the AI to LAWT allowed pulmonary vein isolation with low RF delivery, fluoroscopy, and procedure time while obtaining a high rate of first-pass isolation, in this patient population. Freedom from AF recurrences was as high as in more demanding ablation protocols. A multicentre trial is ongoing to evaluate reproducibility of these results.

A standardized stepwise zero-fluoroscopy approach with transesophageal echocardiography guidance for atrial fibrillation ablation.

PURPOSE: There is growing interest in performing fluoroless radiofrequency ablation (RFA) for atrial fibrillation (AF) due to the increasing awareness of risk associated with radiation exposure of patients and professional staff. The present study aimed to evaluate the feasibility, safety, and efficacy of a stepwise transesophageal echocardiography (TEE)-guided zero-fluoroscopy approach (ZFA) for RFA. METHODS: Consecutive patients (n = 111) referred for AF-ablation were prospectively enrolled with intention to RFA with ZFA. Procedural outcomes were compared with historical controls (HCs) after 1:1 propensity score matching. ZFA success was considered when no X-ray was utilized to perform the whole procedure. RESULTS: ZFA success was achieved in 80 (72%) procedures. BMI > 35 kg/m2 resulted in the only independent predictor of ZFA failure (OR = 6.10, 95% CI 1.15-46.49, p = 0.04). In comparison to HCs, a significant reduction in radiation exposure was observed in the ZFA group: fluoroscopy time (3 vs. 63 s, p < 0.001), total emitted fluoroscopy dose (0.2 vs. 6.0 mGy, p < 0.001), dose area product (0.04 vs. 1.4 Gy*cm2, p < 0.001), and effective dose (0.8 vs. 27.2 mSv*100, p < 0.001). Complete pulmonary vein isolation was achieved in all procedures. No difference was observed between the groups in in-hospital complication rate (0.9% vs. 1.8%, p = 0.99). CONCLUSIONS: This is the largest study proving procedural feasibility, safety, and efficacy of TEE-guided AF-ablation with a complete or near-complete avoidance of radiological exposure, without using intracardiac echocardiography.

Left atrial wall thickness of the pulmonary vein reconnection sites during atrial fibrillation redo procedures.

BACKGROUND: Left atrial wall thickness (LAWT) has been related to pulmonary vein (PV) reconnections after atrial fibrillation (AF) ablation. The aim was to integrate 3D-LAWT maps in the navigation system and analyze the relationship with local reconnection sites during AF-redo procedures. METHODS: Consecutive patients referred for AF-redo ablation were included. Procedure was performed using a single catheter technique. LAWT maps obtained from multidetector computerized tomography (MDCT) were imported into the navigation system. LAWT of the circumferential PV line, the reconnected segment and the reconnected point, were analyzed. RESULTS: Sixty patients [44 (73%) male, age 61 ± 10 years] were included. All reconnected veins were isolated using a single catheter technique with 55 min (IQR 47-67) procedure time and 75 s (IQR 50-120) fluoroscopy time. Mean LAWT of the circumferential PV line was 1.46 ± 0.22 mm. The reconnected segment was thicker than the rest of segments of the circumferential PV line (2.05 + 0.86 vs. 1.47 + 0.76, p < .001 for the LPVs; 1.55 + 0.57 vs. 1.27 + 0.57, p < .001 for the RPVs). Mean reconnection point wall thickness (WT) was at the 82nd percentile of the circumferential line in the LPVs and at the 82nd percentile in the RPVs. CONCLUSION: A single catheter technique is feasible and efficient for AF-redo procedures. Integrating the 3D-LAWT map into the navigation system allows a direct periprocedural estimation of the WT at any point of the LA. Reconnection points were more frequently present in thicker segments of the PV line. The use of 3D-LAWT maps can facilitate reconnection point identification during AF-redo ablation.

Increased rotational flow in the proximal aortic arch is associated with its dilation in bicuspid aortic valve disease.

AIMS: Aortic dilation in bicuspid aortic valve (BAV) might extend to the proximal arch. Arch flow dynamics and their relationship with this segment dilation are still unexplored. Using 4D-flow cardiovascular magnetic resonance, we analysed flow dynamics in the arch for each BAV morphotype and their association with this segment dilation. METHODS AND RESULTS: One hundred and eleven BAV patients (aortic diameters ≤55 mm, non-severe valvular disease), 21 age-matched tricuspid aortic valve (TAV) patients with dilated arch and 24 healthy volunteers (HV) underwent 4D-flow. BAV were classified per fusion morphotype: 75% right-left (RL-BAV), and per arch dilation: 57% dilated, mainly affecting the right-noncoronary (RN) BAV (86% dilated vs. 47% in RL-BAV). Peak velocity, jet angle, normalized displacement, in-plane rotational flow (IRF), wall shear stress, and systolic flow reversal ratio (SFRR) were calculated along the thoracic aorta. ANCOVA and multivariate linear regression analyses were used to identify correlates of arch dilation. BAV had higher rotational flow and eccentricity than TAV in the proximal arch. Dilated compared with non-dilated BAV had higher IRF being more pronounced in the RN-morphotype. RN-BAV, IRF, and SFRR were independently associated with arch dilation. Aortic stenosis and male sex were independently associated with arch dilation in RL-BAV. Flow parameters associated with dilation converged to the values found in HV in the distal arch. CONCLUSION: Increased rotational flow could explain dilation of the proximal arch in RN-BAV and in RL-BAV patients of male sex and with valvular stenosis. These patients may benefit from a closer follow-up with cardiac magnetic resonance or computed tomography.

Influence of Aortic Dilation on the Regional Aortic Stiffness of Bicuspid Aortic Valve Assessed by 4-Dimensional Flow Cardiac Magnetic Resonance: Comparison With Marfan Syndrome and Degenerative Aortic Aneurysm.

OBJECTIVES: This study sought to ascertain whether patients with a bicuspid aortic valve (BAV) have an intrinsic alteration in regional aortic stiffness compared with patients with tricuspid aortic valve (TAV) and Marfan syndrome (MFS) patients with similar aortic sizes, as well as to assess the influence of ascending aorta (AAo) dilation on regional stiffness parameters in BAV patients. BACKGROUND: Imaging biomarkers as predictors of BAV, MFS, and degenerative AAo aneurysms in TAV patients (DA-TAV) are lacking. Biomechanical characterization has been proposed as a possible tool for further aneurysm stratification. METHODS: A total 234 subjects (136 BAV, 44 MFS, and 18 DA-TAV patients and 36 healthy control subjects) were included. The cardiac magnetic resonance protocol comprised 4-dimensional flow to assess AAo and descending aorta (DAo) pulse wave velocities (PWVs) and double-oblique, 2-dimensional, steady-state free-precession cine cardiac magnetic resonance to compute aortic distensibility (AD). RESULTS: On adjusted analysis, nondilated BAV patients had similar PWV and AD as healthy control subjects in both AAo and DAo, whereas dilated BAV did not differ from DA-TAV. In contrast, AAo and DAo stiffness in MFS patients was markedly greater than in BAV patients, increasing slightly with dilation severity. AAo PWV showed a biphasic pattern in BAV patients: it first decreased and then increased throughout AAo dilation, with a clear turning point at 50 mm, whereas distensibility did not discern mildly dilated aorta. In multivariate analysis adjusted for clinical and demographic characteristics, only PWV was related to AAo dilation in BAV patients. CONCLUSIONS: The mechanical properties of AAo aneurysms are similar in BAV and TAV patients, whereas MFS patients have a stiffer aorta. Aortic stiffness strongly depends on dilation severity. AAo PWV resulted in a potentially clinically useful biphasic trend with respect to aneurysm diameter, whereas distensibility did not discern mildly dilated aorta. Beyond clinical risk factors, PWV but not AD was independently related to AAo dilation in BAV patients.

Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease.

BACKGROUND: In patients with bicuspid valve (BAV), ascending aorta (AAo) dilatation may be caused by altered flow patterns and wall shear stress (WSS). These differences may explain different aortic dilatation morphotypes. Using 4D-flow cardiovascular magnetic resonance (CMR), we aimed to analyze differences in flow patterns and regional axial and circumferential WSS maps between BAV phenotypes and their correlation with ascending aorta dilatation morphotype. METHODS: One hundred and one BAV patients (aortic diameter ≤ 45 mm, no severe valvular disease) and 20 healthy subjects were studied by 4D-flow CMR. Peak velocity, flow jet angle, flow displacement, in-plane rotational flow (IRF) and systolic flow reversal ratio (SFRR) were assessed at different levels of the AAo. Peak-systolic axial and circumferential regional WSS maps were also estimated. Unadjusted and multivariable adjusted linear regression analyses were used to identify independent correlates of aortic root or ascending dilatation. Age, sex, valve morphotype, body surface area, flow derived variables and WSS components were included in the multivariable models. RESULTS: The AAo was non-dilated in 24 BAV patients and dilated in 77 (root morphotype in 11 and ascending in 66). BAV phenotype was right-left (RL-) in 78 patients and right-non-coronary (RN-) in 23. Both BAV phenotypes presented different outflow jet direction and velocity profiles that matched the location of maximum systolic axial WSS. RL-BAV velocity profiles and maximum axial WSS were homogeneously distributed right-anteriorly, however, RN-BAV showed higher variable profiles with a main proximal-posterior distribution shifting anteriorly at mid-distal AAo. Compared to controls, BAV patients presented similar WSS magnitude at proximal, mid and distal AAo (p = 0.764, 0.516 and 0.053, respectively) but lower axial and higher circumferential WSS components (p < 0.001 for both, at all aortic levels). Among BAV patients, RN-BAV presented higher IRF at all levels (p = 0.024 proximal, 0.046 mid and 0.002 distal AAo) and higher circumferential WSS at mid and distal AAo (p = 0.038 and 0.046, respectively) than RL-BAV. However, axial WSS was higher in RL-BAV compared to RN-BAV at proximal and mid AAo (p = 0.046, 0.019, respectively). Displacement and axial WSS were independently associated with the root-morphotype, and circumferential WSS and SFRR with the ascending-morphotype. CONCLUSIONS: Different BAV-phenotypes present different flow patterns with an anterior distribution in RL-BAV, whereas, RN-BAV patients present a predominant posterior outflow jet at the sinotubular junction that shifts to anterior or right anterior in mid and distal AAo. Thus, RL-BAV patients present a higher axial WSS at the aortic root while RN-BAV present a higher circumferential WSS in mid and distal AAo. These results may explain different AAo dilatation morphotypes in the BAV population.

Evaluación del flujo retrógrado diastólico en la aorta descendente para cuantificar la insuficiencia aórtica / Descending Aorta Diastolic Retrograde Flow Assessment for Aortic Regurgitation Quantification

Introducción: El flujo diastólico retrógrado en la aorta descendente se ha relacionado con la gravedad de la insuficiencia aórtica; sin embargo, la mayoría de los parámetros vinculados con la velocidad del flujo no se encuentran validados con una técnica de imágenes de referencia. Objetivo: Evaluar la utilidad del flujo retrógrado diastólico en la aorta torácica descendente y la aorta abdominal en la cuan-tificación de la insuficiencia aórtica utilizando como referencia la resonancia magnética. Material y métodos: Se incluyeron 40 pacientes consecutivos en un estudio prospectivo de ecocardiografía y resonancia magnética. Por Doppler pulsado se analizaron los siguientes parámetros: a) la integral velocidad-tiempo del flujo retrógrado diastólico y b) la velocidad máxima telediastólica del flujo regurgitante, ambos en la aorta torácica, y c) el flujo holodiastólico inverso en la aorta abdominal. El protocolo de resonancia magnética incluyó secuencias de contraste de fase para calcular la fracción regurgitante. Valores > 30% se consideraron diagnósticos de insuficiencia aórtica grave. Resultados: Once pacientes (30%) tenían una fracción regurgitante > 30%. La integral velocidad-tiempo del flujo retrógrado diastólico demostró la mayor precisión en el diagnóstico de insuficiencia aórtica grave: ABC = 0,87; p < 0,001. Un punto de corte para la integral velocidad-tiempo del flujo retrógrado diastólico > 15 cm demostró una sensibilidad del 91% y una especificidad del 86% para detectar insuficiencia aórtica grave. El flujo pandiastólico inverso en la aorta abdominal mostró una excelente especificidad (100%) para el diagnóstico de insuficiencia aórtica grave, aunque con baja sensibilidad (50%). Conclusiones: La evaluación del flujo retrógrado diastólico en la aorta torácica descendente permite un diagnóstico adecuado de la insuficiencia aórtica grave. El flujo holodiastólico inverso, aunque es poco sensible, muestra una alta especificidad.

Final results of a phase I-II trial using ex vivo expanded autologous Mesenchymal Stromal Cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration.

BACKGROUND: Cellular therapies have shown encouraging results in the treatment of chronic osteoarthritis (OA). Herein, we present the final results of a phase I-II clinical trial assessing the feasibility, safety and efficacy of ex vivo expanded autologous bone marrow Mesenchymal Stromal Cells (MSC, XCEL-M-ALPHA), infused intra-articularly, in patients with knee OA. METHODS: Fifteen patients (median age=52years) with grade II(9) or III(6) gonarthrosis (Kellgren & Lawrence classification) and chronic pain were treated with an intra-articular infusion of 40.9×10(6)±0.4×10(6) MSCin a phase I-II prospective, open-label, single-dose, single-arm clinical trial. Endpoints were safety and tolerability. Efficacy was measured by the Visual Analogue Scale for pain, algofunctional Health Assessment Questionnaire, Quality of Life (QoL) SF-36 questionnaire, Lequesne functional index and WOMAC score. Cartilage integrity was assessed by Magnetic Resonance Imaging and quantitative T2-mapping at 0, 6 and 12months. RESULTS: The cell-based product was well tolerated with few reported Adverse Events (mild arthralgia and low back pain). There was a relevant decrease in the intensity of pain since day 8 after the infusion, that was maintained after 12months. The SF-36 QoL test showed improvement of parameters including bodily pain, role physical and physical functioning at month 12. The health assessment questionnaire revealed a significant decrease of incapacity. Moreover, T2 mapping showed signs of cartilage regeneration in all patients at 12months post-treatment. CONCLUSIONS: Single intra-articular infusion of XCEL-M-ALPHA is a safe and well-tolerated cell-based product, associated with a long-lasting amelioration of pain, improvement of QoL (up to four years), and signs of cartilage repair.

Differential Diagnosis and Clinical Implications of Remnants of the Right Valve of the Sinus Venosus.

Anatomic variants of the remnants of the right valve of the sinus venosus in adults are common and usually observed on cardiac imaging studies. Because the anatomy and function of these vestiges are not well known, errors may occur in the differential diagnosis and treatment of patients with unclear images in the right atrium. Clinical implications may arise from (1) differential diagnosis with some diseases, especially when the remnants act as sites of attachment for masses; (2) the need for invasive treatment if the anatomic variant displays obstructive behavior; (3) the association between remnants and patent foramen ovale; and (4) secondary complications related to these structures in invasive procedures. Thus, the aim of this review is to provide cardiologists and radiologists specializing in cardiac imaging techniques with the basic anatomic information and clinical implications required to understand morphologic variants of right sinus venosus valve vestiges in adults.

Utility of Real Time 3D Echocardiography for the Assessment of Left Ventricular Mass in Patients with Hypertrophic Cardiomyopathy: Comparison with Cardiac Magnetic Resonance.

INTRODUCTION AND OBJECTIVES: Patients with hypertrophic cardiomyopathy (HCM) have irregular ventricular shapes with small and sometimes obliterated cavities at end-systole that affect the quantification of left ventricular mass (LVM) by conventional methods, such as M-mode or two-dimensional echocardiography. The goal of this study was to validate the use of real time three-dimensional echocardiography (RT3DE) to quantify LVM using cardiac magnetic resonance imaging (CMR) as a reference, in a large population of patients with different types of HCM. METHODS: Forty-eight consecutive patients with HCM had a complete transthoracic examination and CMR performed within 7 days. LVM was calculated by M-mode and RT3DE and compared to CMR that served as gold standard. RESULTS: Left ventricular mass calculated by RT3DE was 195 ± 41 g and 187 ± 49 g by CMR. The correlation between the two methods was moderate, with a Lin index of 0.63 and good linear correlation (r = 0.63, P < 0.0001). The correlation was high when RT3DE was of high or adequate image quality. The correlation between LVM by M-mode and CMR was poor. CONCLUSION: Three-dimensional echocardiography is an accurate method for the quantification of LVM in patients with different subtypes of HCM that is in better agreement with CMR reference values than M-mode measurements.

Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial.

BACKGROUND: Osteoarthritis is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. Conventional treatments demonstrate only modest clinical benefits without lesion reversal. Autologous mesenchymal stromal cell (MSC) treatments have shown feasibility, safety, and strong indications for clinical efficacy. We performed a randomized, active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs, and we obtain information regarding the efficacy of this treatment. METHODS: We randomized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients. The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 10(6) cells. The control group received intra-articular hyaluronic acid (60 mg, single dose). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping. RESULTS: Feasibility and safety were confirmed and indications of clinical efficacy were identified. The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid. Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas, with cartilage quality improvements in MSC-treated patients. CONCLUSIONS: Allogeneic MSC therapy may be a valid alternative for the treatment of chronic knee osteoarthritis that is more logistically convenient than autologous MSC treatment. The intervention is simple, does not require surgery, provides pain relief, and significantly improves cartilage quality.

Influence of dynamic obstruction and hypertrophy location on diastolic function in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a disease with marked genetic and phenotypic heterogeneity. It is well known that obstructive septal forms of this disease entail worse clinical outcome compared with nonobstructive septal and apical forms. The objective of this study was to analyze the differences in left ventricular diastolic function in different subgroups of HCMs and to assess the influence of the location of myocardial hypertrophy and the presence of dynamic obstruction on impairment of diastolic function and its correlation with the clinical status. METHODS: We studied 86 patients with HCM; 27 with the obstructive asymmetric septal type (OAS), 37 with the nonobstructive asymmetric septal type (NOAS) and 22 with apical hypertrophic cardiomyopathy (ApHCM). Patients underwent conventional and tissue Doppler echocardiography and were assessed applying the latest recommendations regarding diastolic dysfunction. Cardiac magnetic resonance was used to study the various morphologic subtypes and quantify left ventricular mass (LVM). RESULTS: The early diastolic annular velocity (e') was significantly lower in OAS with a median of 5 cm/s compared with NOAS with 7 cm/s and ApHCM with 7.5 cm/s (P = 0.0002), and the E/e' ratio was 8.5 in ApHCM, 10 in NOAS and 14 in OAS (P = 0.0001); no significant differences were found in LVM or maximal wall thickness. CONCLUSION: In HCM, the location of left ventricular hypertrophy and the presence of dynamic obstruction affect the degree of diastolic dysfunction; impairment is greater in patients with the OAS type, and markedly less in patients with apical involvement.