Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Brugada ECG phenocopy in hypertrophic cardiomyopathy: The time matter.

An Implantable Cardioverter-Defibrillator was implanted in an asymptomatic 56-year-old man, with type 2 Brugada pattern on ECG, inducible ventricular fibrillation at elective electrophysiological study, and a family history of sudden cardiac death. Seventeen years later, the patient was admitted to the hospital due to palpitations related to a typical atrial flutter. A transthoracic echocardiogram unexpectedly revealed a clinically manifest hypertrophic cardiomyopathy.

Left bundle branch area pacing in a young athlete with progressive cardiac conduction (Lev-Lenegre) disease.

We present the case of a professional soccer player affected by right bundle branch block and symptomatic 2:1 atrio-ventricular block during effort, due to progressive cardiac conduction disease (Lev-Lenegre disease), who received successful left bundle branch area pacing after a failed attempt at His bundle pacing. The electrocardiographic outcome of paced QRS was consistent with a rapid electrical activation of the left ventricle through the Purkinje system. The pursue of physiological pacing was preferred over conventional, given the young age of our patient and the expectedly high burden of stimulation, to reduce the long-term risk of pacing-induced cardiomyopathy.

Complementary effectiveness of carotid sinus massage and tilt testing for the diagnosis of reflex syncope in patients older than 40 years: a cohort study.

AIMS: Indications, methodology, and diagnostic criteria for carotid sinus massage (CSM) and tilt testing (TT) have been standardized by the 2018 Guidelines on Syncope of the European Society of Cardiology. Aim of this study was to assess their effectiveness in a large cohort which reflects the performance under 'real-world' conditions. METHODS AND RESULTS: We analysed all patients who had undergone CSM and TT in the years 2003-2019 for suspected reflex syncope. Carotid sinus massage was performed according to the 'Method of Symptoms'. Tilt testing was performed according to the 'Italian protocol' which consists of a passive phase followed by a sublingual nitroglycerine phase. For both tests, positive test was defined as reproduction of spontaneous symptoms in the presence of bradycardia and/or hypotension. Among 3293 patients (mean age 73 ± 12 years, 48% males), 2019 (61%) had at least one test positive. A bradycardic phenotype was found in 420 patients (13%); of these, 60% were identified by CSM, 37% by TT, and 3% had both test positive. A hypotensive phenotype was found in 1733 patients (53%); of these, 98% were identified by TT and 2% had both TT and CSM positive. CONCLUSION: The overall diagnostic yield of the tests in patients >40-year-old with suspected reflex syncope was 61%. Both CSM and TT are useful for identifying those patients with a bradycardic phenotype, whereas CSM has a limited value for identifying the hypotensive phenotype. Since the overlap of responses between tests is minimal, both CSM and TT should be performed in every patient over 40 years receiving investigation for unexplained but possible reflex syncope.

Reproducibility of carotid sinus massage.

AIMS: The reproducibility of carotid sinus massage (CSM) is debated. The aim of this study was to assess the reproducibility according to the methodology and diagnostic criteria defined by the guidelines on syncope of the European Society of Cardiology. METHOD: Among 2800 patients with syncope who underwent CSM in the years 2005-2019, 109 patients (62 males; mean age 76 ± 10 years) had performed a second CSM after a median of 28 months. Carotid sinus hypersensitivity (CSH) was diagnosed when CSM elicited a pause of >3 s and/or a fall in systolic blood pressure >50 mm Hg without reproduction of spontaneous symptoms. Carotid sinus syndrome (CSS) was established when spontaneous symptoms were reproduced in the presence of bradycardia and/or hypotension. RESULTS: The reproducibility of CSM was 78% for 18 CSS patients, 41% for 29 CSH patients, and 77% for 62 negative patients. The corresponding interrater agreement was good for CSS (kappa = 0.66), moderate for negative CSM (kappa = 0.42), and poor for CSH (kappa = 0.30). Combining CSH and negative tests, their reproducibility rose to 90% with kappa = 0.66. CONCLUSION: CSS but not CSH has a good reproducibility. About half of patients with CSH had a negative response at the second test, thus suggesting a great overlap between them.

Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration.

Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 µg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/ß-catenin signalling pathway activation. In fact, δ-TT increased ß-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/ß-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of ß-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound.

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Long-Term Results After Single and Multiple Procedures of Ablation of Ventricular Tachycardia.

INTRODUCTION: The aim of this study was to assess long-term results after single and multiple procedures of catheter ablation of ventricular tachycardia (VT). While it is generally accepted that multiple procedures are sometimes necessary in order to achieve long-term clinical success, the literature on this issue displays wide variability. METHODS: We assessed the outcome of 160 consecutive patients who underwent 214 ablation procedures in the period 2008 to May 2015: 93 had overt structural heart disease (SHD) (previous myocardial infarction in 74 cases) and 67 had no SHD. RESULTS: After the first procedure, the 1-year actuarial recurrence rates were 25% in patients with SHD and 5% in those without. However, recurrences increased progressively after the first year, reaching 46% and 35%, respectively, at 5 years. Overall, VT recurred in 35/93 (38%) patients with SHD and 22/67 (33%) patients without. Redo (1 to 4) procedures were performed in 28 (20%) patients with SHD and 18 (27%) patients without. After the last procedure, the 1-year actuarial recurrence rates were 5% in patients with SHD and 7% in those without, and the corresponding rates at 5 years were 23% and 7%. During follow-up, 21 patients died (all in the SHD group): no death was related to VT recurrence. CONCLUSIONS: During long-term follow-up, VT frequently recurs after the first procedure, both in patients with SHD and in those without; multiple procedures are needed in order to increase the success rate.

Syncope in patients paced for atrioventricular block.

AIMS: Although syncope is the main reason for cardiac pacing in ∼40% of patients affected by atrioventricular block (AVB), very few data are available on the benefit of cardiac pacing in preventing syncopal recurrences. METHODS AND RESULTS: We retrospectively evaluated 229 consecutive patients (124 males, age 80 ± 10 years) who had received a permanent pacemaker from January 2009 to December 2013 for AVB and syncope (94 patients, 41%) or AVB without syncope (135 patients, 59%). In patients with AVB and syncope, a third-degree or Mobitz II second-degree AVB had been documented in 73 and was only suspected in another 21, all of whom had bundle branch block. Follow-up was available in 223 patients. At 5 years, the actuarial syncope recurrence rate was 1% (95% CI, 0-3) in patients with documented AVB plus syncope and 3% (95% CI, 1-5) in those without syncope, whereas it was 14% (95% CI, 0-28) in patients with undocumented AVB plus syncope (P = 0.001). The actuarial combined recurrence rate of syncope and/or pre-syncope was 2% (95% CI, 0-4) in patients without syncope, 8% (95% CI, 0-17) in patients with documented AVB plus syncope, and 19% (95% CI, 1-37) in patients with undocumented AVB plus syncope, P = 0.002. All syncopes occurred in patients without overt structural heart disease (SHD), the corresponding actuarial estimate being 4% (95% CI, 0-6) at 1 year and 6% (95% CI, 4-8) at 5 years (P = 0.002 vs. patients with SHD). CONCLUSIONS: Cardiac pacing is highly effective in preventing syncopal recurrences when AVB is documented. Syncope may recur in a non-negligible minority of paced patients when AVB is suspected but not documented and in patients without SHD.

Long-Term Outcome of Patients with Bifascicular Block and Unexplained Syncope Following Cardiac Pacing.

BACKGROUND: According to the ACC/AHA/HRS guidelines, cardiac pacing is reasonable in patients with bifascicular block (BF-B) and syncope when other causes have been excluded. The purpose of this study was to assess the long-term outcome of patients with BF-B and unexplained syncope following cardiac pacing. METHODS AND RESULTS: Between 2009 and 2015, we identified 43 consecutive patients (mean age of 78 ± 12 years, 64% males) who presented with syncope and BF-B and had received a pacemaker (PM). During a mean follow-up period of 31 ± 21 months, syncope recurred in seven patients (16%): 7% (95% standard error [SE] ± 3%) at 1 year and 18% (95% SE ± 7%) at 5 years. At univariable analysis, the only predictor of syncope recurrence was empiric pacing (P = 0.03). There were no syncope recurrences in the 12 patients who received a PM following a positive electrophysiological study (EPS) and the five patients with documentation of paroxysmal atrioventricular block (AVB) during cardiac monitoring (insertable loop recorder [ILR]), (EPS/ILR Group, n = 17) compared to seven of 26 (27%) patients who received empiric pacing (Empiric Group, n = 26; P = 0.02). Progression to high-degree AVB was documented during follow-up in 16 (37%) patients: nine of 17 (53%) patients in the EPS/ILR Group and seven of 26 (27%) patients in the Empiric Group (P = 0.11). There were no injuries reported during ILR monitoring. CONCLUSIONS: We have shown that syncope recurs not infrequently in patients with BF-B who received pacing for syncope. Nearly one in four patients who had empiric pacing suffered syncope recurrence compared to no recurrences in patients who received a PM following a positive EPS or documentation of transient AVB.

Long-term clinical outcome of patients who failed catheter ablation of atrial fibrillation.

AIMS: Left atrial ablation fails to prevent symptomatic recurrences of atrial fibrillation (AF) in 20-30% of patients up to 3 years of follow-up despite multiple procedures. Data are lacking on the long-term clinical outcome of those patients for whom the decision was taken to renounce performing further ablation procedures. METHODS AND RESULTS: In this multicentre study, 218 (34%) of 631 consecutive patients, who had undergone AF catheter ablation in the years 2001-11 for drug-refractory symptomatic AF, had symptomatic AF recurrences after 1.5 ± 0.6 procedures. Their long-term clinical outcome was assessed in March 2012 (minimum follow-up 1 year). At a mean of 5.1 ± 2.6 years since their last ablation, 82 (38%) patients improved, 103 (47%) remained unchanged and 33 (15%) worsened, but only 17 (8%) had such a severe impairment of their quality of life as to require atrioventricular junction ablation and pacing (#13) or cardiac surgery (#4); 22 (10%) patients had had adverse clinical events (death in five, heart failure in five, stroke and transient ischaemic cerebral attack in four, severe haemorrhage in four, pacemaker or implantable cardioverter-defibrillator implantation in seven) and 98 (45%) patients had developed permanent AF. Compared with patients without permanent AF, fewer patients with permanent AF improved (3% vs. 66%, P = 0.001) and more got worse (28% vs. 5%, P = 0.001). At multivariable logistic regression, single ablation procedure, left atrial diameter, persistent AF and time from the last ablation were independent predictors of permanent AF. CONCLUSION: More than 5 years after a failed AF ablation, a small minority of patients had such an impaired quality of life as to require non-pharmacological interventions. Almost half developed permanent AF, which significantly impaired quality of life. Permanent AF was more common in patients who had left atrial enlargement, history of persistent AF, longer follow-up, and had performed a single ablation procedure, thus hypothesizing that reablation could reduce the chronicization of arrhythmia. A low risk of stroke was observed in the long-term follow-up.

Clinical context and outcome of carotid sinus syndrome diagnosed by means of the 'method of symptoms'.

AIMS: The prevalence and outcome of carotid sinus syndrome (CSS) reported in the literature vary owing to differences in indications and methods of carotid sinus massage (CSM). METHODS AND RESULTS: We performed CSM on all patients aged 40 years and above with unexplained syncope after the initial evaluation. Carotid sinus massage was performed in the supine and standing positions on both sides for 10 s during continuous electrocardiogram and blood pressure monitoring; CSS was diagnosed in the event of an abnormal response to CSM in association with reproduction of spontaneous symptoms ('method of symptoms'). From July 2005 to July 2012, CSS was found in 164 (8.8%) of 1855 patients (mean age 77 ± 9 years, 73% males): 81% had an asystolic reflex (mean pause 7.6 ± 2.2 s) and 19% a vasodepressor reflex (mean lowest systolic blood pressure 65 ± 15 mmHg). Potential multifactorial causes of syncope (orthostatic hypotension, bundle branch block, bradycardia, tachyarrhythmias) were found in 74% of patients. One hundred forty-one patients received the proper care [advice on lifestyle measures in all, discontinuation (#40) or reduction (#17) of antihypertensive drugs, pacemaker implantation (#57)] and were followed up for 39 ± 25 months. Syncope recurred in 23 patients; the actuarial syncopal recurrence rate was 7% at 1 year and 26% at 5 years. Total syncopal episodes decreased from 91 per year during the 2 years before evaluation to 21 episodes per year during follow-up (P = 0.001). On Cox proportional-hazards regression, a mixed or vasodepressor response to tilt testing was the only independent predictor of syncopal recurrence (hazard ratio = 1.8; P = 0.01). CONCLUSION: Carotid sinus massage by means of the 'method of symptoms' indentifies a clinical syndrome with definite features and outcome. A treatment strategy involving lifestyle measures, reduction of antihypertensive drugs and cardiac pacing when appropriate is effective in reducing the syncopal recurrence rate.

Additional diagnostic value of implantable loop recorder in patients with initial diagnosis of real or apparent transient loss of consciousness of uncertain origin.

AIMS: Non-syncopal transient loss of consciousness (T-LOC) encompasses disorders that sometimes resemble syncope, and the differential diagnosis with true syncope may be challenging. The implantable loop recorder (ILR) is potentially useful, but has never been systematically assessed. The aim of the study is to evaluate the diagnostic value of ILR in distinguishing syncope from non-syncopal forms of T-LOC. METHODS AND RESULTS: We implanted an ILR in 58 patients (mean age 71 ± 17 years, 25 males) who had had 4.6 ± 2.3 episodes of real or apparent T-LOC, in order to distinguishing epilepsy from syncope (#28), unexplained fall from syncope (#29), or functional pseudo-syncope from syncope (#1). During 20 ± 13 months of follow-up, 33 patients (57%) had a spontaneous event documented by ILR. A diagnosis of syncope was established by ILR documentation of an arrhythmia in 15 (26%) patients: an asystole of 6 s (IQR 4-10 s) duration was documented at the time of the spontaneous event in seven patients with initial suspicion of epilepsy and in five patients with unexplained fall; atrial tachyarrhythmia was documented at the time of the spontaneous event in 1 and 1 patient, respectively, and ventricular tachycardia in 1 patient with unexplained fall. Conversely, in another 18 patients, ILR monitoring documented no significant rhythm abnormalities at the time of T-LOC recurrence, thus excluding an arrhythmic syncope. Finally, ILR was unable to document any syncopal episode in 25 (43%) patients. Among the 15 patients with an established diagnosis of arrhythmic syncope, syncope recurred during follow-up in 2 of 11 patients who were on pacemaker therapy and in 3 of 4 patients who were on other therapies. CONCLUSION: Implantable loop recorder monitoring provides additional diagnostic value in 'difficult' patients with an initial diagnosis of non-syncopal real or apparent T-LOC.

Altered expression of 3-betahydroxysterol delta-24-reductase/selective Alzheimer's disease indicator-1 gene in Huntington's disease models.

INTRODUCTION: 3-betahydroxysterol delta-24-reductase (DHCR24), also called selective Alzheimer's disease indicator-1, is a crucial enzyme in cholesterol biosynthesis with neuroprotective properties that is downregulated in brain areas affected by Alzheimer's disease. AIM: In the present study, we investigated modifications of DHCR24 expression in models of Huntington's disease (HD), a neurodegenerative disorder caused by a polyglutamine expansion in huntingtin (Htt) protein that induces degeneration of cerebral cortex and striatum as well as lateral hypothalamic abnormality. METHODS: Basal expression of DHCR24 and its modulation after oxidative stress were evaluated in rat striatal precursors cells (ST14A) transfected with wild-type (Htt) or mutant Htt (mHtt) and in brain tissue of an HD mouse model (R6/2). RESULTS: The results showed that DHCR24 transcript levels were decreased in ST14A cells expressing mHtt and in the brain of symptomatic R6/2 mice, but were significantly increased in ST14A cells overexpressing wild-type Htt. In addition, we demonstrated that, in the striatal precursors, the decrease of DHCR24 expression in response to oxidative stress was modified according to the presence of Htt or of its mutant form. Preliminary results indicated a modification of DHCR24 expression in post-mortem brain samples of HD patients. CONCLUSIONS: In conclusion, these results support the hypothesis of a possible role of DHCR24 in HD.

Targets for deprescribing in patients with hypertension and reflex syncope.

BACKGROUND: We aimed to identify the target of deprescribing, i.e. the 24-hour SBP increase needed to achieve the greatest reduction of SBP drops. METHOD: Forty hypertensive patients (mean age 73.6 ± 9.3 years, 26 females) with reflex syncope and SBP drops on a screening ABPM were advised to withdraw or to reduce their therapy. The study objective was the reduction of SBP drops <90 mmHg and <100 mmHg on a second ABPM performed within 3 months. RESULTS: Out of a total of 98 drugs taken during ABPM 1, 44 were withdrawn, 16 had a dose reduction and 38 remained unchanged at the time of ABPM 2. 24-hour SBP increased from 119.7 ± 10.1 mmHg to 129.4 ± 13.2 mmHg during ABPM2. Total disappearance of daytime SBP drops <100 mmHg was achieved in 20 (50 %) patients who had 24-hour SBP of 134±13 mmHg and an increase from ABPM 1 of 12 (IQR 5-20) mmHg. Compared with the 20 patients who had persistence of drops, these patients had a greater reduction of the number of hypotensive drugs (67 % versus 19 %, p = 0.002) and a greater rate of withdrawals (62 % versus 29 %, p = 0.003). CONCLUSION: In hypertensive patients with reflex syncope, an increase of 12 mmHg and an absolute value of 24-hour SBP of 134 mmHg appear to represent the optimal goals aimed to prevent SBP drops. Drugs withdrawal, rather than simply dose reduction, is mostly required to achieve the above target.

Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism.

Kallmann syndrome (KS) is a genetic disease characterized by hypogonadotropic hypogonadism and impaired sense of smell. The genetic causes underlying this syndrome are still largely unknown, but are thought to be due to a developmental defect in the migration of gonadotropin-releasing hormone (GnRH) neurons. Understanding the causes of the disease is hampered by lack of appropriate mouse models. GnRH neurons are hypothalamic cells that centrally control reproduction in mammals by secreting the GnRH decapeptide into the portal blood vessels of the pituitary to stimulate the production of gonadotropins. During development, these cells are born in the nasal placode outside the brain and migrate in association with olfactory/vomeronasal axons to reach the forebrain and position themselves in the hypothalamus. By combining the analysis of genetically altered mice with in vitro models, we demonstrate here that a secreted guidance cue of the class 3 semaphorin family, SEMA3A, is essential for the development of the GnRH neuron system: loss of SEMA3A signalling alters the targeting of vomeronasal nerves and the migration of GnRH neurons into the brain, resulting in reduced gonadal size. We found that SEMA3A signals redundantly through both its classical receptors neuropilin (NRP) 1 and, unconventionally, NRP2, while the usual NRP2 ligand SEMA3F is dispensable for this process. Strikingly, mice lacking SEMA3A or semaphorin signalling through both NRP1 and NRP2 recapitulate the anatomical features of a single case of KS analysed so far, and may therefore be used as genetic models to elucidate the pathogenesis of KS.

Physiological and pharmacological overview of the gonadotropin releasing hormone.

Gonadotropin-Releasing Hormone (GnRH) is a decapeptide responsible for the control of the reproductive functions. It shows C- and N-terminal aminoacid modifications and two other distinct isoforms have been so far identified. The biological effects of GnRH are mediated by binding to high-affinity G-protein couple receptors (GnRHR), showing characteristic very short C tail. In mammals, including humans, GnRH-producing neurons originate in the embryonic nasal compartment and during early embryogenesis they undergo rapid migration towards the hypothalamus; the increasing knowledge of such mechanisms improved diagnostic and therapeutic approaches to infertility. The pharmacological use of GnRH, or its synthetic peptide and non-peptide agonists or antagonists, provides a valid tool for reproductive disorders and assisted reproduction technology (ART). The presence of GnRHR in several organs and tissues indicates additional functions of the peptide. The identification of a GnRH/GnRHR system in the human endometrium, ovary, and prostate has extended the functions of the peptide to the physiology and tumor transformation of such tissues. Likely, the activity of a GnRH/GnRHR system at the level of the hippocampus, as well as its decreased expression in mice brain aging, raised interest in its possible involvement in neurogenesis and neuronal functions. In conclusion, GnRH/GnRHR appears to be a fascinating biological system that exerts several possibly integrated pleiotropic actions in the complex control of reproductive functions, tumor growth, neurogenesis, and neuroprotection. This review aims to provide an overview of the physiology of GnRH and the pharmacological applications of its synthetic analogs in the management of reproductive and non-reproductive diseases.

The Role of Fecal Microbiota Transplantation in the Allogeneic Stem Cell Transplant Setting.

Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy.

Rate and nature of complications of conduction system pacing compared with right ventricular pacing: Results of a propensity score-matched analysis from a multicenter registry.

BACKGROUND: Conduction system pacing (CSP) using His bundle pacing (HBP) or left bundle branch area pacing (LBBAP) has emerged as an alternative to right ventricular pacing (RVP). Comparative data on the risk of complications between CSP and RVP are lacking. OBJECTIVE: This prospective, multicenter, observational study aimed to compare the long-term risk of device-related complications between CSP and RVP. METHODS: A total of 1029 consecutive patients undergoing pacemaker implantation with CSP (including HBP and LBBAP) or RVP were enrolled. Propensity score matching for baseline characteristics yielded 201 matched pairs. The rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the 2 groups. RESULTS: During a mean follow-up duration of 18 months, device-related complications were observed in 19 patients: 7 in RVP (3.5%) and 12 in CSP (6.0%) (P = .240). On dividing the matched cohort into 3 groups with similar baseline characteristics according to pacing modality (RVP, n = 201; HBP, n = 128; LBBAP, n = 73), patients with HBP showed a significantly higher rate of device-related complications than did patients with RVP (8.6% vs 3.5%; P = .047) and patients with LBBAP (8.6% vs 1.3%; P = .034). Patients with LBBAP showed a rate of device-related complications similar to that of patients with RVP (1.3% vs 3.5%; P = .358). Most of the complications observed in patients with HBP (63.6%) were lead related. CONCLUSION: Globally, CSP was associated with a risk of complications similar to that of RVP. Considering HBP and LBBAP separately, HBP showed a significantly higher risk of complications than did both RVP and LBBAP whereas LBBAP showed a risk of complications similar to that of RVP.

Additional diagnostic value of very prolonged observation by implantable loop recorder in patients with unexplained syncope.

INTRODUCTION: In the literature, the average diagnostic yield of the implantable loop recorder (ILR) is reported to be 35% over an observation period generally less than 18 months. The aim of this study was to evaluate the diagnostic value of ILR during very prolonged observation. METHODS AND RESULTS: Consecutive patients who had received one or more (in the case of battery exhaustion before diagnosis) ILR (Reveal/plus/DX, Medtronic Inc.) from 2001 to 2010 were included. The diagnostic ECG was classified according to the ISSUE classification. We analyzed 157 patients (87 males, 69 ± 14 years): 70 of these were followed up for ≥18 months. The estimated cumulative diagnostic rates were 30%, 43%, 52%, and 80% at 1, 2, 3, and 4 years, respectively; 26% of diagnoses were made after 18 months. The diagnostic yield was independent of structural heart disease, bundle branch block, number of syncopes, age, and gender; the median time to diagnosis of ISSUE type 1 patients was shorter than that of the others (4 [2;10] vs. 16 [6;23] months; P = 0.003). During the observation period, 3 patients (1.9%) died and none suffered arrhythmic death. CONCLUSIONS: Prolonging observation up to 4 years increased the diagnostic value of ILR in syncopal patients and was safe. A quarter of patients diagnosed needed more than 18 months of follow-up. As consequence, when a strategy of prolonging monitoring is chosen, monitoring should be maintained even for several years until diagnosis is established.