Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Arbovirus surveillance on the Mexico-USA border: West Nile virus identification in various species of field mosquitoes.

West Nile virus (WNV) has been documented in human and/or mosquito samples near the border with Mexico in El Paso, Texas, and Doña Ana County, New Mexico. However, on the Mexican side of the border, particularly in the State of Chihuahua, no such cases of WNV-infected mosquitoes have been documented. We tested 367 mosquitoes of four species (Culex quinquefasciatus, Cx. tarsalis, Aedes aegypti, and Aedes (Ochlerotatus) epactius) and found a high rate of WNV-positivity, including the first record of Ae. (Ochlerotatus) epactius infection with WNV. These results call for intensifying WNV surveillance efforts on the border between the United States and Mexico, with particular emphasis on vector control and monitoring of the species included in this study.

Twenty-five years of research on syncope.

Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.

Tilt testing remains a valuable asset.

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.

First national record of Aedes melanimon (Diptera: Culicidae) in Mexico.

Aedes (Ochlerotatus) melanimon Dyar 1924 has been considered an important pest in agricultural and rural communities. Aedes melanimon is a vector of WEEV and CEV and is a competent laboratory vector of WNV. The known range of Ae. melanimon extends throughout Southwest Canada, part of Central and most of Western USA. Here we report the first record of Ae. melanimon in Mexico, at Ciudad Juárez, Chihuahua. The collect represents the southernmost distributional record for this species. Its indigenous presence in a highly urbanized and dry area was not expected. A permanent surveillance program to detect and determine the species in border-crossing cities is encouraged.

Urban regeneration policies and mental health in a context of economic crisis in Andalusia (Spain).

Literature suggests that urban regeneration policies might contribute towards improving mental health of residents, but to date there is a lack of empirical research on how these policies and downward social mobility can interact and influence health outcomes. The current study aims to explicitly test whether regeneration policies implemented in deprived Andalusian urban places (southern Spain) moderate the use of anxiolytics and/or antidepressants, taking into consideration families' downward social mobility during the recent period of economic crisis in Spain. We designed a post intervention survey to retrospectively compare the evolution of psychotropic drug consumption in target and comparison areas. We observe a general increase in the use of anxiolytics and/or antidepressants from 2008 to 2015, specifically for people in whose families the economic crisis had the greatest impact (odds ratio = 2.18; p value < 0.001). However, better evolution is observed among residents of the target areas compared with residents of similar urban areas where this kind of polices have been not in force (odds ratio = 0.50; p value < 0.05). Therefore, urban regeneration policies might act as moderators of the risk of mental health, particularly when people are subject to the loss of individual/family resources in urban vulnerable contexts.

The benefit of pacemaker therapy in patients with neurally mediated syncope and documented asystole: a meta-analysis of implantable loop recorder studies.

Aim: Although the efficacy of cardiac pacing in patients with neurally mediated syncope (NMS) and documented asystole is established, a more robust point estimate of the benefit, which is not possible with any individual study, is lacking. Methods and results: We undertook a meta-analysis of individual participant data from four studies that reported follow-up data on syncope recurrence with cardiac pacing in patients with NMS who had had an electrocardiographic (ECG) documentation of an asystolic event by means of implantable loop recorder (ILR). Of a total of 1046 patients, who had ILR implanted, 383 (36.6%) patients had an ECG documentation of a diagnostic event during mean follow-up of 13 ± 10 months. Of these, 201 (52%) patients, corresponding to 19.2% of the total ILRs, had an asystolic event of 12.8 ± 11.0 s duration documented and met the criteria for pacemaker therapy. Follow-up was available in 121 (60%) of those patients with asystolic events. Syncope recurred after pacing in 18 (14.9%) patients with an actuarial rate of 13% [95% confidence interval (CI) ±6] at 1 year, 21% (95%CI ±10) at 2 years, and 24% (95%CI ±11) at 3 years. On multivariable Cox regression analysis, positive tilt test response was the only significant predictor of syncope recurrence with a hazard ratio (95% CI) of 4.3 (1.4-13). On the contrary, type of asystolic event (sinus arrest or atrioventricular block), prodrome, cardiac abnormalities, number and duration of history of syncope, age, and gender were not predictors of recurrence of syncope. Conclusion: A long asystolic pause, suitable for pacemaker therapy, was found in one of five patients with ILR. After pacemaker implantation, most of these patients remained free of syncope recurrence for up to 3 years. The benefit of pacemaker was greater in patients with negative tilt test.

Selective Angiography Using the Radiofrequency Catheter: An Alternative Technique for Mapping and Ablation in the Aortic Cusps.

BACKGROUND: Ablation in aortic cusps could be necessary in up to 15% of the patients, especially in para-Hisian atrial tachycardia and ventricular arrhythmias arising from outflow tracts. Risk of coronary damage has led to recommendation of systematic coronary angiography (CA) during the procedure. Other image tests as intravascular (ICE) or transesophageal echocardiography (TEE) have been proposed. Both methods have limitations: additional vascular access for ICE and need for additional CA in some patients in case of TEE. We describe an alternative method to assess relation of catheter tip and coronary ostia during ablation in aortic cusps without additional vascular accesses by performing selective angiography with the ablation catheter. METHODS AND RESULTS: We prospectively evaluated 12 consecutive patients (69.3 ± 8.5, 6 female) who underwent ablation in right (1), left (5), and noncoronary cusps (6). We performed angiography through the ablation cooled tip radiofrequency catheter at the ablation site. Ablation was effective in 91.6% of the patients (3 patients needed additional ablation out of coronary cusps: pulmonary cusp, right ventricular outflow tract (RVOT), and coronary sinus and 1 patient underwent a second procedure because recurrence). No complications occurred neither during procedure nor follow-up (6.2 ± 3.8 months). No technical problems occurred with the ablation catheter after contrast injection. CONCLUSION: Selective angiography through a cooled-tip radiofrequency ablation catheter is feasible to assess relation of coronary ostia and ablation site when ablation in aortic cusps. It allows continuous real-time assessment of this relation, avoids the need for additional vascular accesses and no complications occurred in our series.

Transfusion management and immunohematologic complications in liver transplantation: experience of a single institution.

OBJECTIVE: Liver transplantation (LT) has traditionally been associated with major blood loss and consequently high blood transfusion requirements. Our objective was to analyze transfusion management and incidence of immunohematologic complications in patients undergoing LT at our institution. METHODS: A retrospective analysis of immunohematologic events and transfusion outcomes was carried out at La Fe University Hospital in Valencia. Data from 654 patients were reviewed: 654 underwent only one LT while 36 underwent second LT. RESULTS: Patients received a median of 3 red blood cell (RBC) concentrates, 2 platelets concentrates (PCs) and 2 fresh frozen plasma units (FFPs). Variables significantly influencing RBC transfusions were: the MELD score, hemoglobin levels, and the platelet counts before LT. 27 patients (4.1%) had a positive antibody screening before transplant. Immunohematologic events occurred in 8% of the patients, mostly in the first month after LT, and involved hemolysis in 13 cases. Mortality was significantly higher in patients developing immunohematologic disorders (42.8 vs. 18.3%; p < 0.001). In the multivariable analysis, only ABO minor incompatibility between donor and recipient significantly increased the appearance of immunohematologic incidences (OR 4.92, 95% CI 2.31-10.50; p < 0.001). CONCLUSION: Transfusion management of patients that underwent LT can be complicated by immunohematologic problems. Blood banks should implement the DAT test in each transfusion to detect them.

Physical counter-pressure manoeuvres in preventing syncopal recurrence in patients older than 40 years with recurrent neurally mediated syncope: a controlled study from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)†.

AIMS: Physical counter-pressure manoeuvres (PCM) are effective in young patients with vasovagal syncope and recognizable prodromal symptoms. The aim of this study was to investigate their effectiveness in patients ≥40 years with severe neurally mediated syncope (NMS) enroled in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3). METHODS AND RESULTS: In the ISSUE-3 study, 63 out of 162 patients had a diagnosis of hypotensive NMS (Types 2, 3, and 4A) documented by implantable loop recorder; of these, 40 were instructed to perform isometric leg and arm PCM therapy. Their mean age was 62 ± 13 years; 47% of patients had a history of some episodes without prodrome. A group of 45 untreated patients acted as controls. The primary endpoint was the time to first syncope recurrence. During follow-up, syncope recurred in 15 PCM patients (37%) and in 24 control patients (53%) (P = 0.14). At 21 months, the modelled syncope recurrence rates were 42% [95% confidence interval (CI): 27-61] and 64% (95% CI: 48-80), respectively (P = 0.27). CONCLUSION: In conclusion, many ISSUE-3 patients affected by hypotensive NMS have syncopal recurrence despite PCM. Older age and the absence of sufficiently long recognizable prodromal symptoms in the ISSUE-3 population might have hampered the effectiveness of PC therapy.

Cardiac pacing in patients with neurally mediated syncope and documented asystole: effectiveness analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) Registry.

AIMS: The randomized, double-blind Third International Study on Syncope of Uncertain Etiology (ISSUE-3) showed that dual-chamber permanent pacing was effective in reducing the recurrence of syncope in patients ≥ 40 years with severe asystolic, probably neurally mediated syncope (NMS), documented by implantable loop recorder (ILR). Analysis in ISSUE-3 was performed according to the intention-to-treat principle. In the present study, we performed an on-treatment analysis, which included additionally those non-randomized patients followed up in the ISSUE registry to evaluate in a better manner the effectiveness of cardiac pacing therapy. METHODS AND RESULTS: Initially, 504 patients received an ILR, 162 (32%) patients had a diagnosis consistent with NMS within a mean observation period of 15 ± 11 months: 99 (19%) patients had documentation of syncope with ≥ 3 s asystole or ≥ 6 s asystole without syncope. Sixty patients affected by asystolic NMS received cardiac pacing therapy and 86 (33 asystolic and 53 non-asystolic NMS) were untreated; 16 patients were lost to follow-up. Paced and unpaced groups had similar clinical characteristics. During subsequent follow-up, syncope recurred in 10 paced (17%) and in 40 non-paced (46%) patients. At 21 months, the estimated product-limit syncope recurrence rates were 27% [95% confidence interval (CI) 15-47] and 54% (95% CI 43-67), respectively (P = 0.01). With cardiac pacing, the risk of recurrence was reduced by 57% (hazard ratio = 0.43, 95% CI = 0.2-0.8). Complications of pacemaker therapy were haemothorax at implantation in one patient and lead dislodgement that required correction in two patients. CONCLUSION: Permanent cardiac pacing is effective in reducing recurrence of syncope in patients ≥ 40 years with severe asystolic possible NMS with a few complications. The study shows that 61% of patients with a diagnosis of NMS made by ILR received a pacemaker but 5.1 ILRs had to be implanted to find one patient who finally had a pacemaker implanted.

Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Long-term outcome of 'long-term liver transplant survivors'.

There are few studies focusing on long-term complications in liver transplant (LT) recipients. The aim of this study was to define the outcome of LT recipients having survived at least 10 years from LT. Of 323 adult LT done between 1991 and 1997, the 167(52%) alive >10 years post-LT (baseline time) formed the study population. Long-term outcome measures included the following: immunosuppression, metabolic complications [obesity, arterial hypertension (AH), diabetes, dislypidemia], cardiovascular events (CVE), chronic renal dysfunction-CRD, and de novo tumors. Median age at LT was 50 years. Most common indication was postnecrotic cirrhosis (89%), mostly because of HCV (46%). At study-baseline (10 years post-LT), 29% were obese and AH, diabetes, dislypidemia, and CRD were present in 75%, 30%, 42%, and 36%, respectively. In most cases, these complications were already present 1 year post-LT; less than one quarter developed them onward. The 6 year cumulative survival since baseline reached 84% (n = 24 deaths), with most deaths related to recurrent graft diseases (mostly HCV) followed by de novo tumors or CVE. 1, 3, 5 and 10 years cumulative rates of CVE and de novo tumors since baseline were 2%, 5%, 10% and 17%, and 1%, 3%, 6% and 13%, respectively. Chronic renal impairment was independently associated with survival and development of CVE since baseline. The medium-term survival of 'long-term survivors', i.e. patients alive 10 years after LT is good, but metabolic complications and CRD are common and continue to increase afterwards. Cardiovascular events and de novo tumors increase gradually over time and represent a major cause of late mortality.

Comparison of results of combined liver-kidney transplantation vs. isolated liver transplantation.

INTRODUCTION: Combined liver-kidney transplantation (LKT) is the best therapeutic option for patients with end-stage liver and kidney disease. OBJECTIVES: To analyze baseline characteristics and clinical outcome of LKT compared to isolated liver transplantation (LT). MATERIAL AND METHODS: The study included 16 LKT performed between 1998 and 2006 and 32 LT matched by age, sex, date and indication for transplantation. Demographic, pretransplant, post-transplant and survival variables were analyzed. RESULTS: As planned by the study design, mean age, distribution by sex and indication for LT were similar between groups. The most common indication for LT was HCV- and/or alcohol-induced cirrhosis. The most common indication for KT was renal failure, in most cases secondary to glomerulonephritis. Twelve patients (69%) were on dialysis before LKT. Hepatocellular carcinoma and diabetes mellitus pre-transplantation were similar between groups. However pretransplant arterial hypertension (AHT) was higher in LKT than LT (50% vs. 19%; p = 0.02). In the post-transplant: reoperation due to bleeding, bacterial infections, liver rejection, AHT and median creatinine levels at 1st and 3rd years were similar in LKT and LT. In contrast, early post-transplant dialysis was higher in LKT than LT (31% vs. 3%; p = 0.01). Survival rates at 1st, 3rd, 5th and 7th years were similar in both groups (87.5%, 74%, 74% and 66% vs. 81%, 75%, 75% and 75% in LT and LKT, respectively). CONCLUSIONS: LKT is an effective therapeutic option in patients with end-stage liver and kidney disease. Most early and late complications and long-term survival are similar to those observed with LT.

Mechanism substitution in preventive innovations: Dissecting the reproduction of health inequalities in the United States.

In the last three decades, numerous studies in different countries have corroborated the main postulates of the Fundamental Cause Theory (FCT), providing evidence showing how health inequalities are reproduced as society increases its capacity to control disease and/or avoid its consequences through preventive innovations. However, documenting the reproductive logic proposed by the theory requires the development of a dynamic analytical approach to consider socioeconomic disparities in the incorporation of multiple preventive innovations over time, which could act as mediating mechanisms of the durable relationship between socioeconomic status and health/mortality. This study draws on data from different waves of the National Health Interview Survey and the National Health and Nutrition Examination Survey to analyze the diffusion processes of various innovations in the U.S. The results of the study show that educational inequalities emerge, are amplified, and are reduced by the continuous diffusion of preventive innovations, supporting the meta-hypothesis of substitution of mediating mechanisms according to the interconnections of FCT and Diffusion of Innovation Theory.

Diagnosis, management, and outcomes of patients with syncope and bundle branch block.

AIMS: Although patients with syncope and bundle branch block (BBB) are at high risk of developing atrio-ventricular block, syncope may be due to other aetiologies. We performed a prospective, observational study of the clinical outcomes of patients with syncope and BBB following a systematic diagnostic approach. METHODS AND RESULTS: Patients with ≥1 syncope in the last 6 months, with QRS duration ≥120 ms, were prospectively studied following a three-phase diagnostic strategy: Phase I, initial evaluation; Phase II, electrophysiological study (EPS); and Phase III, insertion of an implantable loop recorder (ILR). Overall, 323 patients (left ventricular ejection fraction 56 ± 12%) were studied. The aetiological diagnosis was established in 267 (82.7%) patients (102 at initial evaluation, 113 upon EPS, and 52 upon ILR) with the following aetiologies: bradyarrhythmia (202), carotid sinus syndrome (20), ventricular tachycardia (18), neurally mediated (9), orthostatic hypotension (4), drug-induced (3), secondary to cardiopulmonary disease (2), supraventricular tachycardia (1), bradycardia-tachycardia (1), and non-arrhythmic (7). A pacemaker was implanted in 220 (68.1%), an implantable cardioverter defibrillator in 19 (5.8%), and radiofrequency catheter ablation was performed in 3 patients. Twenty patients (6%) had died at an average follow-up of 19.2 ± 8.2 months. CONCLUSION: In patients with syncope, BBB, and mean left ventricular ejection fraction of 56 ± 12%, a systematic diagnostic approach achieves a high rate of aetiological diagnosis and allows to select specific treatment.

[The preventive efforts of the Spanish autonomous regions and socio-economic inequality in childhood obesity or overweight]. / Los esfuerzos preventivos de las comunidades autónomas y la desigualdad socioeconómica en la obesidad o el sobrepeso infantil.

OBJECTIVE: To explore trends in childhood overweight/obesity according to socio-economic status and in relation to the preventive effort developed by the Spanish autonomous regions. METHOD: A series of multilevel cross-sectional studies were conducted using data from different waves of the Spanish National Health Survey, namely 2003, 2006, 2011 and 2017. Hierarchical logistic regression models were estimated, with individuals (level 1) nested within the region-period of study (level 2) and these, in turn, within the region (level 3). The main independent variables were the average effort made by the Spanish autonomous regions in child overweight-obesity prevention policies and the change in the effort made in these policies over the periods studied. RESULTS: The likelihood of obesity and/or overweight increases substantially if the adult respondent in the household is also obese or overweight. The joint effect of the policies implemented by the autonomous regions is associated with a significant decrease in prevalence only for children belonging to high and middle social classes (odds ratio [OR]: 0.89, 95% confidence interval [95%CI]: 0.82-0.96, and OR: 0.93, 95%CI: 0.88-0.97, respectively). CONCLUSIONS: The policies implemented by the Spanish autonomous regions seem to have a limited capacity to achieve significant reductions in the prevalence of childhood overweight and obesity. The results suggest that it is the middle and upper-middle class groups that seem to benefit most from these policies, which could indirectly contribute to increasing inequalities in childhood obesity.