Mechanism-based therapy of non-cardiac syncope: a practical guide.

The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.

The triggers of situational syncope do not influence the Head-up Tilt Test response and prognosis.

OBJECTIVE: The study evaluated the positivity rate, hemodynamic responses, and prognosis in terms of syncopal recurrence among patients with situational syncope (SS) stratified according to the underlying situational triggers. METHODS: We retrospectively evaluated all consecutive patients with SS who underwent nitroglycerin (NTG)-potentiated HUTT at Syncope Unit of the University of Campania "Luigi Vanvitelli" - Monaldi Hospital from March 1st, 2017, to May 1st, 2023. All patients were followed for at least one year. The study population was divided according to the underlying triggers (micturition, swallow, defecation, cough/sneeze, post-exercise). RESULTS: 236 SS patients (mean age 50± 19.3 years; male 63.1%) were enrolled; among them, the situational trigger was micturition in 109 patients (46.2%); swallow in 32 (13.6%) patients; defecation in 35 (14.8%) patients; post-exercise in 41 (17.4%) patients and cough/sneeze in 17 (7.2%) patients. There were no significant differences in baseline clinical characteristics and HUTT responses between different situational triggers. The Kaplan-Meier analysis did not show a statistically different rate of syncope recurrence across patients stratified by baseline situational triggers (log-rank p=0.21). CONCLUSIONS: SS appears to be a homogenous syndrome and different triggers do not impact the HUTT response or syncope recurrence at 1 year.

Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope.

AIMS: A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex. METHODS AND RESULTS: Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12 b.p.m. and systolic blood pressure (SBP) was 108 ± 19 mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14 b.p.m. within a median of 0.1 min [inter-quartile range (IQR), 0.1-0.7 min] when the SBP was 99 ± 21 mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17 mmHg and the CLS rate was 95 ± 13 b.p.m. The onset of CLS pacing was 1.7 min (IQR, 1.5-3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0 min (IQR, 3.3-8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22 mmHg at baseline to 69 ± 4 mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1 b.p.m.). CONCLUSION: The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect. REGISTRATION: ClinicalTrials.gov identifier: NCT06038708.

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.

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.

Asystole on loop recorder in patients with unexplained syncope and negative tilt testing: age distribution and clinical predictors.

BACKGROUND: Approximately 50% of patients with unexplained syncope and negative head-up tilt test (HUTT) who have an electrocardiogram (ECG) documentation of spontaneous syncope during implantable loop recorder (ILR) show an asystolic pause at the time of the event. OBJECTIVE: The aim of the study was to evaluate the age distribution and clinical predictors of asystolic syncope detected by ILR in patients with unexplained syncope and negative HUTT. METHODS: This research employed a retrospective, single-center study of consecutive patients. The ILR-documented spontaneous syncope was classified according to the International Study on Syncope of Uncertain Etiology (ISSUE) classification. RESULTS: Among 113 patients (54.0 ± 19.6 years; 46% male), 49 had an ECG-documented recurrence of syncope during the observation period and 28 of these later (24.8%, corresponding to 57.1% of the patients with a diagnostic event) had a diagnosis of asystolic syncope at ILR: type 1A was present in 24 (85.7%), type 1B in 1 (3.6%), and type 1C in 3 (10.7%) patients. The age distribution of asystolic syncope was bimodal, with a peak at age < 19 years and a second peak at the age of 60-79 years. At Cox multivariable analysis, syncope without prodromes (OR 3.7; p = 0.0008) and use of beta blockers (OR 3.2; p = 0.002) were independently associated to ILR-detected asystole. CONCLUSIONS: In patients with unexplained syncope and negative HUTT, the age distribution of asystolic syncope detected by ILR is bimodal, suggesting a different mechanism responsible for asystole in both younger and older patients. The absence of prodromes and the use of beta blockers are independent predictors of ILR-detected asystole.

Short-duration head-up tilt test potentiated with sublingual nitroglycerin in suspected vasovagal syncope: the fast Italian protocol.

BACKGROUND: The traditional nitroglycerin (NTG) head-up tilt test (HUTT) is time-consuming and the test duration is a barrier to widespread utilization in clinical practice. It was hypothesized that a short-duration protocol is not inferior to the traditional protocol regarding the positivity rate and has a similar distribution of hemodynamic response. METHODS AND RESULTS: Patients undergoing HUTT were randomized 1:1 to a 10 min passive phase plus a 10 min 0.3 mg NTG if the passive phase was negative (Fast) or to a 20 min passive phase plus a 15 min 0.3 mg NTG if the passive phase was negative (Traditional). A sample size of 277 patients for each group achieved 80% power to detect an expected difference of 0% with a non-inferiority margin of -10% using a one-sided t-test and assuming a significant level alpha of 0.025. A total of 554 consecutive patients (mean age 46.6 ± 19.3 years, 47.6% males) undergoing HUTT for suspected vasovagal syncope were randomly assigned to the Fast (n = 277) or Traditional (n = 277) protocol. A positive response was defined as the induction of syncope in presence of hypotension/bradycardia, and was observed in 167 (60.3%) patients with Fast and in 162 (58.5%) patients with the Traditional protocol. There was a trend of lesser vasodepressor response (14.8% Fast vs. 20.6% Traditional) which was significant during the passive phase (P = 0.01). CONCLUSION: The diagnostic value of the Fast HUTT protocol is similar to that of the Traditional protocol and therefore the Fast protocol can be used instead of the Traditional protocol.

Twenty-year experience of atrial fibrillation ablation: a single-centre cohort study.

AIMS: While several studies in the literature have reported results of catheter ablation of AF, few is known regarding outcome for more than 10 years. METHODS AND RESULTS: The complete population of patients who underwent AF ablation in the years 2002-2021 in the department of cardiology of the hospital of Reggio Emilia has been analysed. The last follow-up was made in the second half of 2022. During this period the technique of ablation remained relatively unchanged as well the physicians performing ablation. Primary endpoint was the recurrence of symptomatic AF, defined as AF that caused symptoms that were defined by the patient as able to alter their quality of life. 669 patients underwent catheter ablation and 618 were followed until 2022. Median age of the patients was 58 ± 9 years and 521 (78%) were male. There were 407 (61%) of patients with paroxysmal AF, 167 (25%) with persistent AF and 95 (14%) with long-lasting AF. A total of 838 procedures were performed, with a mean of 1.25 per patient. 163 (26%) patients had 2 procedures and 6 had 3 ablations. Periprocedural complications occurred in 4.8% of procedures. Follow-up data were available for 618 patients (92.4%). The median follow-up duration was 6.6 years (IQR 3.2-10.8). The estimated recurrence rate of symptomatic AF was 26% at 10 years, 54% at 15 years and 82% at 20 years. The recurrence rate was similar in patients who had performed one procedure and in those who had performed 2 or 3 procedures. Progression to permanent AF occurred in 112 patients (18%). The major events that occurred during the follow-up consisted of total mortality in 4.5%, heart failure in 3.1% and TIA/stroke in 2.4%. CONCLUSION: Symptomatic AF tends to recur during long-term follow-up despite one or more procedures. Catheter ablation seems able to reduce the rate of symptomatic recurrences and to delay the time of their occurrence. These findings are consistent with the knowledge that an age-dependent progressive structural atriomiopathy is the basis for the development of AF.

Definitive aetiology of unexplained syncope after cardiovascular autonomic tests in a tertiary syncope unit.

AIMS: Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. METHODS AND RESULTS: Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. CONCLUSION: A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.

A novel and practical method to add video monitoring to tilt table testing.

AIMS: We describe a novel, practical, and inexpensive method to add video recording during tilt table testing (TTT): Open-Access-Video-TTT. METHODS AND RESULTS: The Open-Access-Video-TTT set-up uses a personal computer (PC) to capture screen video data from a non-invasive-beat-to-beat (NIBTB) haemodynamic blood pressure (BP) device, combined with video recording of a patient, using Open Broadcaster Software (OBS®). The new Open-Access-Video-TTT set up was tested with both the Finometer (model Finapres Nova®, Medical Systems, the Netherlands) and the Task Force® Touch Cardio monitor (CNSystems, Austria). For this, the Finapres Nova® was enabled in 'remote' mode and Real Video Network Computing (RealVNC®) was installed on the PC/laptop. The Task Force® has a DisplayPort (DP) port, for which a DP/ high-definition multimedia interface (HDMI) cable and a video capture card is used to merge the signals to the PC/laptop. With this method the combined images are stored as a new video signal. TTT can be performed with any routine protocol. CONCLUSIONS: Open Access-Video-TTT worked well for both the Finapres NOVA® and the Task Force Monitor ®. This novel method can be used easily by all physicians who wish to add video recording during TTT who do not have access to an electroencephalogram machine.

Prevalence of asystole during tilt test-induced vasovagal syncope may depend on test methodology.

This review addresses tilt-testing methodology by searching the literature which reports timing of asystole and loss of consciousness (LOC). Despite the Italian protocol being the most widely adopted, its stipulations are not always followed to the letter of the European Society of Cardiology guidelines. The discrepancies permit reassessment of the incidence of asystole when tilt-down is early, impending syncope, compared with late, established LOC. Asystole is uncommon with early tilt down and diminishes with increasing age. However, if LOC is established as test-end, asystole is more common, and it is age-independent. Thus, the implications are that asystole is commonly under-diagnosed by early tilt-down. The prevalence of asystolic responses observed using the Italian protocol with a rigorous tilt down time is numerically close to that observed during spontaneous attacks by electrocardiogram loop recorder. Recently, tilt-testing has been questioned as to its validity but, in selection of pacemaker therapy in older highly symptomatic vasovagal syncope patients, the occurrence of asystole has been shown to be an effective guide for treatment. The use of head-up tilt test as an indication for cardiac pacing therapy requires pursuing the test until complete LOC. This review offers explanations for the findings and their applicability to practice. A novel interpretation is offered to explain why pacing induced earlier may combat vasodepression by raising the heart rate when sufficient blood remains in the heart.

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.

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.

Early and late-onset syncope: insight into mechanisms.

AIMS: Unexplained syncope is an important clinical challenge. The influence of age at first syncope on the final syncope diagnosis is not well studied. METHODS AND RESULTS: Consecutive head-up tilt patients (n = 1928) evaluated for unexplained syncope were stratified into age groups <30, 30-59, and ≥60 years based on age at first syncope. Clinical characteristics and final syncope diagnosis were analysed in relation to age at first syncope and age at investigation. The age at first syncope had a bimodal distribution with peaks at 15 and 70 years. Prodromes (64 vs. 26%, P < 0.001) and vasovagal syncope (VVS, 59 vs. 19%, P < 0.001) were more common in early-onset (<30 years) compared with late-onset (≥60 years) syncope. Orthostatic hypotension (OH, 3 vs. 23%, P < 0.001), carotid sinus syndrome (CSS, 0.6 vs. 9%, P < 0.001), and complex syncope (>1 concurrent diagnosis; 14 vs. 26%, P < 0.001) were more common in late-onset syncope. In patients aged ≥60 years, 12% had early-onset and 70% had late-onset syncope; older age at first syncope was associated with higher odds of OH (+31% per 10-year increase, P < 0.001) and CSS (+26%, P = 0.004). Younger age at first syncope was associated with the presence of prodromes (+23%, P < 0.001) and the diagnoses of VVS (+22%, P < 0.001) and complex syncope (+9%, P = 0.018). CONCLUSION: In patients with unexplained syncope, first-ever syncope incidence has a bimodal lifetime pattern with peaks at 15 and 70 years. The majority of older patients present only recent syncope; OH and CSS are more common in this group. In patients with early-onset syncope, prodromes, VVS, and complex syncope are more common.

Association between hypotension during 24†h ambulatory blood pressure monitoring and reflex syncope: the SynABPM 1 study.

AIMS: Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. The study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM. METHODS AND RESULTS: ABPM data from reflex syncope patients and controls, matched by average 24 h SBP, age, sex, and hypertension were compared. Patients with constitutional hypotension, orthostatic hypotension, and predominant cardioinhibition during carotid sinus massage or prolonged electrocardiogram monitoring or competing causes of syncope were excluded. Daytime and nighttime SBP drops (<110, 100, 90, 80 mmHg) were assessed. Findings were validated in an independent sample. In the derivation sample, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drops <90 mmHg achieved 91% specificity and 32% sensitivity [odds ratio (OR) 4.6, P < 0.001]. Two or more daytime drops <100 mmHg achieved 84% specificity and 40% sensitivity (OR 3.5, P = 0.001). Results were confirmed in the validation sample of 164 syncope patients and 164 controls: one or more daytime SBP drops <90 mmHg achieved 94% specificity and 29% sensitivity (OR 6.2, P < 0.001), while two or more daytime SBP drops <100 mmHg achieved 83% specificity and 35% sensitivity (OR 2.6, P < 0.001). CONCLUSION: SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.

Theophylline in patients with syncope without prodrome, normal heart, and normal electrocardiogram: a propensity-score matched study verified by implantable cardiac monitor.

AIMS: Syncope without prodromes in subjects with normal heart and normal electrocardiogram (ECG) is classified as non-classical neurally mediated syncope and is characterized by low adenosine plasma levels (APLs) and frequent asystolic syncope. We assessed the efficacy of theophylline, a non-selective adenosine receptor antagonist, in preventing syncopal events. METHODS AND RESULTS: Participants received an implantable cardiac monitor, underwent APL measurement, and received oral theophylline at maximum tolerated dose (starting dose 300 mg b.i.d.). They were compared with a historical cohort of untreated patients with implantable cardiac monitor who had the same inclusion criteria and were balanced with the propensity score (PS) method as regard age, sex, lifetime syncopal episodes, APL, and antihypertensive drugs. Primary endpoint was time to first syncopal recurrence at 24 months. There were 76 patients in the theophylline group and 58 in the control group. Syncope recurred in 25 (33%) patients in the theophylline group and in 27 (47%) patients in the control group, with an estimated 2-year recurrence rate of 33% and 60%, respectively, and a hazard ratio of 0.53 [95% confidence interval (CI), 0.30-0.95; P = 0.034]. Most of the benefit of theophylline is derived from reduction of syncope due to asystolic atrioventricular (AV) block (hazard ratio of 0.13; 95% CI, 0.03-0.58; P = 0.008). Thirty (39%) patients discontinued theophylline after a median of 6.4 (interquartile range 1.7-13.8) months due to side effects. CONCLUSION: Theophylline was effective in preventing recurrences in patients with syncope without prodromes, normal heart, and normal ECG. The benefit was greater in patients with syncope due to asystolic AV block. CLINICALTRIALS.GOV IDENTIFIER: NCT03803215.

Cardioinhibitory syncope with asystole during nitroglycerin potentiated head up tilt test: prevalence and clinical predictors.

AIMS: The aim of our study was to evaluate the prevalence and clinical predictors of cardioinhibitory (CI) responses with asystole at the nitroglycerin (NTG)-potentiated head-up tilt test (HUTT) in patients with a history of syncope admitted to a tertiary referral syncope unit. METHODS: We retrospectively evaluated all consecutive patients who underwent NTG-potentiated HUTT for suspected reflex syncope at our institution from March 1 2017 to May 1 2020. The prevalence of HUTT-induced CI syncope was assessed. Univariate and multivariate analyses were performed to test the association of asystolic response to HUTT with a set of clinical covariates. RESULTS: We enrolled 1285 patients (45 ± 19.1 years; 49.6% male); 368 (28.6%) showed HUTT-induced CI response with asystole. A multivariate analysis revealed that the following factors were independently associated with HUTT-induced CI syncope: male sex (OR 1.48; ConInt 1.14-1.92; P = 0.003), smoking (OR 2.22; ConInt 1.56-3.115; P < 0.001), traumatic syncope (OR: 2.81; ConInt 1.79-4.42; P < 0.001), situational syncope (OR 0.45; ConInt 0.27-0.73; P = 0.002), and the use of diuretics (OR 9.94; ConInt 3.83-25.76; P < 0.001). CONCLUSIONS: The cardioinhibitory syncope with asystole induced by NTG-potentiated HUTT is more frequent than previously reported. The male gender, smoking habit, history of traumatic syncope, and use of diuretics were independent predictors of HUTT-induced CI responses. Conversely, the history of situational syncope seems to reduce this probability.

Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole.

AIM: The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial. METHODS AND RESULTS: We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%). CONCLUSION: In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing. STUDY REGISTRATION: ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546.

AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial.

AIMS: In patients with atrial fibrillation (AF) and heart failure (HF), strict and regular rate control with atrioventricular junction ablation and biventricular pacemaker (Ablation + CRT) has been shown to be superior to pharmacological rate control in reducing HF hospitalizations. However, whether it also improves survival is unknown. METHODS AND RESULTS: In this international, open-label, blinded outcome trial, we randomly assigned patients with severely symptomatic permanent AF >6 months, narrow QRS (≤110 ms) and at least one HF hospitalization in the previous year to Ablation + CRT or to pharmacological rate control. We hypothesized that Ablation + CRT is superior in reducing the primary endpoint of all-cause mortality. A total of 133 patients were randomized. The mean age was 73 ± 10 years, and 62 (47%) were females. The trial was stopped for efficacy at interim analysis after a median of 29 months of follow-up per patient. The primary endpoint occurred in 7 patients (11%) in the Ablation + CRT arm and in 20 patients (29%) in the Drug arm [hazard ratio (HR) 0.26, 95% confidence interval (CI) 0.10-0.65; P = 0.004]. The estimated death rates at 2 years were 5% and 21%, respectively; at 4 years, 14% and 41%. The benefit of Ablation + CRT of all-cause mortality was similar in patients with ejection fraction (EF) ≤35% and in those with >35%. The secondary endpoint combining all-cause mortality or HF hospitalization was significantly lower in the Ablation + CRT arm [18 (29%) vs. 36 (51%); HR 0.40, 95% CI 0.22-0.73; P = 0.002]. CONCLUSIONS: Ablation + CRT was superior to pharmacological therapy in reducing mortality in patients with permanent AF and narrow QRS who were hospitalized for HF, irrespective of their baseline EF. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT02137187.

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.