Cardiac Pacing in Cardioinhibitory Reflex Syncope: Clinical Use of Closed-loop Stimulation.

Cardiac pacing has been studied extensively in patients with reflex syncope over the past two decades. The heterogeneity of the forms and clinical manifestations of reflex syncope explain the controversial results of older randomised clinical trials. New evidence from recent trials has changed medical practice, now leading to clear indications for pacing in patients with asystolic syncope documented during carotid sinus massage, implantable cardiac monitoring or tilt testing. Given that recent trials in reflex syncope have been performed using the closed-loop stimulation algorithm, the authors will briefly discuss this pacing mode, review hypotheses about the mechanisms underlying its activation during syncope and provide practical instructions for programming and troubleshooting.

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.

P-Wave Amplitude and PR Changes in Patients With Inappropriate Sinus Tachycardia: Findings Supportive of a Central Mechanism.

BACKGROUND: The mechanism of inappropriate sinus tachycardia (IST) remains incompletely understood. METHODS AND RESULTS: We prospectively compared 3 patient groups: 11 patients with IST (IST Group), 9 control patients administered isoproterenol (Isuprel Group), and 15 patients with cristae terminalis atrial tachycardia (AT Group). P-wave amplitude in lead II and PR interval were measured at a lower and higher heart rate (HR1 and HR2, respectively). P-wave amplitude increased significantly with the increase in HR in the IST Group (0.16±0.07 mV at HR1=97±12 beats per minute versus 0.21±0.08 mV at HR2=135±21 beats per minute, P=0.001). The average increase in P-wave amplitude in the IST Group was similar to the Isuprel Group (P=0.26). PR interval significantly shortened with the increases in HR in the IST Group (146±15 ms at HR1 versus 128±16 ms at HR2, P<0.001). A similar decrease in the PR interval was noted in the Isuprel Group (P=0.6). In contrast, patients in the atrial tachycardia Group experienced PR lengthening during atrial tachycardia when compared with baseline normal sinus rhythm (153±25 ms at HR1=78±17 beats per minute versus 179±29 ms at HR2=140±28 beats per minute, P<0.01). CONCLUSIONS: We have shown that HR increases in patients with IST were associated with an increase in P-wave amplitude in lead II and PR shortening similar to what is seen in healthy controls following isoproterenol infusion. The increase in P-wave amplitude and absence of PR lengthening in IST support an extrinsic mechanism consistent with a state of sympatho-excitation with cephalic shift in sinus node activation and enhanced atrioventricular nodal conduction.

Assessment of a standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncopes.

AIMS: Opinions differ regarding the effectiveness of cardiac pacing in patients affected by reflex syncope. We assessed a standardized guideline-based algorithm in different forms of reflex syncope. METHODS AND RESULTS: In this prospective, multi-centre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncopes, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker. POPULATION: 253 patients, mean age 70 ± 12 years, median 4 (3-6) syncopes, 89% without or with short prodromes. Of these patients, 120 (47%) received a pacemaker and 106 were followed up for a mean of 13 ± 7 months: syncope recurred in 10 (9%). The recurrence rate was similar in 61 CSM+ (11%), 30 TT+ (7%), and 15 ILR+ (7%) patients. The actuarial total syncope recurrence rate was 9% (95% confidence interval (CI), 6-12) at 1 year and 15% (95% CI, 10-20) at 2 years and was significantly lower than that observed in the group of 124 patients with non-diagnostic tests who had received an ILR: i.e. 22% (95% CI, 18-26) at 1 year and 37% (95% CI, 30-43) at 2 years (P = 0.004). CONCLUSION: About half of older patients with severe recurrent syncopes without prodromes have an asystolic reflex for which cardiac pacing goes along with a low recurrence rate. The study supports the clinical utility of the algorithm for the selection of candidates to cardiac pacing in everyday clinical practice. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01509534.

Assessment of the vasodepressor reflex in carotid sinus syndrome.

BACKGROUND: Assessment of the vasodepressor reflex in carotid sinus syndrome is influenced by the method of execution of the carotid sinus massage and the coexistence of the cardioinhibitory reflex. METHODS AND RESULTS: Carotid sinus massage reproduced spontaneous symptoms in 164 patients in the presence of hypotension or bradycardia (method of symptoms). When an asystolic pause was induced, the vasodepressor reflex was reassessed after suppression of the asystolic reflex by means of 0.02 mg/kg IV atropine. An isolated vasodepressor form was found in 32 (20%) patients, who had lowest systolic blood pressure (SBP) of 65±15 mm Hg. Of these, only 21 (66%) patients had an SBP fall ≥50 mm Hg, which is the universally accepted cut-off value for the diagnosis of the vasodepressor form. Conversely, a lowest SBP value of ≤85 mm Hg (corresponding to the fifth percentile) detected 97% of vasodepressor patients, but was also present in 84% of the 132 patients with an asystolic reflex. These latter patients had both asystole ≥3 s (mean 7.6±2.2 s) and SBP fall to 63±22 mm Hg: in 46 (28%) patients, symptoms persisted after atropine (mixed form), in the remaining 86 (52%) patients, symptoms did not (cardioinhibitory form) persist. CONCLUSIONS: The current definition of ≥50 mm Hg SBP fall failed to identify one third of patients with isolated vasodepressor form. A cut-off value of symptomatic SBP of ≤85 mm Hg seems more appropriate, but it is unable to identify cardioinhibitory forms. In asystolic forms, atropine testing is able to distinguish a cardioinhibitory form from a mixed form.

Vagally mediated atrioventricular block: pathophysiology and diagnosis.

Vagally mediated atrioventricular (AV) block is defined as a paroxysmal AV block, localised within the AV node, associated with slowing of the sinus rate. All types of second-degree AV block, including pseudo-Mobitz II block, and complete AV block, may be present. Most of the patients have normal AV conduction. Differential diagnosis with intrinsic AV block is based on the behaviour of the sinus rate. Vagally mediated AV block is benign; it can be recorded as an asymptomatic or symptomatic event (syncope/presyncope). Syncope due to this form of AV block should be diagnosed and managed as neurally mediated syncope. When this block is fortuitously recorded in asymptomatic patients, pacemaker implantation is not indicated.

Resynchronization of the left ventricular contraction by tailored programming of right and left ventricular pacing.

AIMS: The prerequisite and the rationale for the benefit of cardiac resynchronization therapy (CRT) is that it is able to resynchronize left ventricular (LV) walls that have a delayed activation. METHODS AND RESULTS: In 69 consecutive patients who underwent biventricular (BIV) pacemaker implantation, we assessed the magnitude of intraventricular resynchronization achieved by means of simultaneous (BIV 0) and sequential BIV pacing (with an individually optimized VV interval value among +80 ms and -80 ms) using pulsed-wave tissue Doppler imaging techniques and in particular the measurement of the intra-LV electromechanical delay. The intra-LV delay was defined as the difference between the longest and the shortest activation time in the six basal segments of the LV. An abnormal intra-LV delay was defined as a value >41 ms. The intra-LV delay was 63 +/- 28 ms baseline, decreased to 44 +/- 26 ms with BIV 0 and to 26 +/- 15 ms with optimized BIV (P = 0.001). BIV 0 determined the shortest delay in 28 (41%) patients (23 +/- 12 ms). In 41 (59%) patients, a better resynchronization was achieved with optimized VV intervals (LV first in 32 and RV first in 5) or single-chamber pacing (LV in 3 and RV in 1). With BIV 0, the intra-LV delay remained abnormal in 41% and was longer than baseline in 30% of patients compared with 9 and 12% with optimized BIV, respectively (P = 0.001). CONCLUSION: A sub-optimal resynchronization is achieved with simultaneous BIV pacing in most patients. A tailored programming of the relative contribution of RV and LV pacing forms the prerequisite for improving CRT results.

Two unusual cases of coincident atrioventricular nodal reentrant tachycardia and ventricular tachycardia.

The simultaneous occurrence of narrow and wide QRS complex tachycardias was observed in 2 patients evaluated at our electrophysiological centers. Electrophysiological testing revealed the coexistence of two types of arrhythmia (atrioventricular nodal reentrant tachycardia and verapamil-sensitive left ventricular tachycardia) in one patient and of three types of arrhythmia (atrioventricular nodal reentrant tachycardia, ventricular tachycardia originating from the right ventricular outflow tract, and left ventricular tachycardia) in the other. Both patients underwent successful radiofrequency ablation of all the types of tachycardia.

[How is syncope studied in the Italian hospitals?]. / Come viene studiata la sincope negli ospedali italiani? Risultati del primo "Censimento Nazionale dei Centri per lo studio della sincope".

BACKGROUND: The aim of this study was to evaluate how the main tests for the diagnostic assessment of syncope are currently performed in the Italian hospitals. METHODS: During the early 2003 dedicated questionnaires were administered to about 400 Italian hospitals. About each test information was requested relative to: test protocol, laboratory equipment, patients evaluated during 2002. RESULTS: Eighty-four hospitals answered the questionnaire. A syncope-dedicated ambulatory (at least once a week) was available during 2002 in 59/84 hospitals, and 56 were dependent on the Cardiology Division. Carotid sinus massage was performed either in clinostatic and in orthostatic position in 60 Centers and was repeated after atropine in 15. To define the test positivity, 35 Centers followed the "symptom method". Only 15 Centers performed > 100 procedures during 2002 (range 3-500). Tilt testing was performed in 72 hospitals. A dedicated tilting bed was available in 65 Centers, continuous beat-to-beat pressure measurement in 22. Out of the 72 Centers, 55 followed the so-called "Italian protocol" as the main methodology of the test. Only 17 Centers performed > 100 procedures during 2002 (range 3-500). Adenosine test was performed in 26 hospitals, the median dose of drug was 18 mg (range 6-20 mg); 25 out 26 Centers considered the test as positive when an asystolic pause > or = 6 s was observed. Only 6 Centers performed > 15 procedures during 2002 (range 1-204). An implantable loop recorder was available in 48 Centers. The number of implant procedures during 2002 varied among the Centers from 1 to 22. CONCLUSIONS: A great variability was observed concerning the methodology of each test and the number of procedures performed. Thus, a standardization effort about the methodology of syncope study is still needed by the medical associations.

Efficacy and feasibility of isometric arm counter-pressure manoeuvres to abort impending vasovagal syncope during real life.

AIMS: Isometric arm exercises are able to increase blood pressure during the phase of impending vasovagal syncope. We evaluated their efficacy and feasibility during daily life in a group of 29 consecutive patients affected by vasovagal syncopes. METHODS: The patients were trained to use arm tensing and/or handgrip in case of occurrence of symptoms of impending syncope. RESULTS: During 14+/-6 months of follow-up, 260 episodes of impending syncope were reported by 19 patients; the manoeuvres were self-administered by these patients in 98% of cases and were able to abort syncope in 99.6% of cases. Overall, 5 episodes of syncope occurred in 5 patients (17%), in 4 cases without and in 1 with activation of the manoeuvres. Syncope recurred in 4 (40%) of 10 patients aged >65 years versus only 1 (5%) of 19 patients aged < or =65 years, p=0.03. The non-responders had more episodes of impending syncope than responders (37+/-32 vs 3+/-4, p=0.001). Among 19 clinical variables, age in years was the only significant predictor of syncopal recurrence. No patients had injury or other adverse morbidity related to the relapses. CONCLUSIONS: Isometric arm counter-pressure manoeuvres are able to abort impending vasovagal syncope in most patients aged < or =65 years. Arm counter-pressure manoeuvres are feasible, safe and well accepted by the patients in the daily life.

Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope.

OBJECTIVES: We hypothesized that isometric arm exercises were able to increase blood pressure (BP) during the phase of impending vasovagal syncope and allow the patient to avoid losing consciousness. BACKGROUND: Hypotension is always present during the prodromal phase of vasovagal syncope. METHODS: We evaluated the effect of handgrip (HG) and arm-tensing in 19 patients affected by tilt-induced vasovagal syncope. The study consisted of an acute single-blind, placebo-controlled, randomized, cross-over tilt-table efficacy study and a clinical follow-up feasibility study. RESULTS: In the acute tilt study, HG was administered for 2 min, starting at the time of onset of symptoms of impending syncope. In the active arm, HG caused an increase in systolic blood pressure (SBP) from 92 +/- 10 mm Hg to 105 +/- 38 mm Hg, whereas in the placebo arm SBP decreased from 91 +/- 11 mm Hg to 73 +/- 21 mm Hg (p = 0.008). Heart rate behavior was similar in the two arms. In the active arm, 63% of patients became asymptomatic, versus 11% in the control arm (p = 0.02); conversely, only 5% of patients developed syncope, versus 47% in the control arm (p = 0.01). The patients were trained to self-administer arm-tensing treatment as soon as symptoms of impending syncope occurred. During 9 +/- 3 months of follow-up, the treatment was actually performed in 95/97 episodes of impending syncope (98%) and was successful in 94/95 (99%). No patients suffered injury or other adverse morbidity related to the relapses. CONCLUSIONS: Isometric arm contraction is able to abort impending vasovagal syncope by increasing systemic BP. Arm counter-pressure maneuvers can be proposed as a new, feasible, safe, and well accepted first-line treatment for vasovagal syncope.

Mechanism of syncope in patients with heart disease and negative electrophysiologic test.

BACKGROUND: In patients with syncope and structural heart disease, syncope is suspected to be attributable to a primary cardiac arrhythmia, but little is known of its mechanism when electrophysiologic study is unremarkable. METHODS AND RESULTS: We applied an implantable loop recorder in 35 patients with overt heart disease at risk of ventricular arrhythmia, because these were patients with previous myocardial infarction or cardiomyopathy with depressed ejection fraction or nonsustained ventricular tachycardia in whom an electrophysiologic study was unremarkable. During a follow-up of 3 to 15 months, syncope recurred in 6 patients (17%) after a mean of 6+/-5 months; in 3 patients, the mechanism of syncope was bradycardia with long pauses (sudden-onset AV block in 2 cases and sinus arrest in 1 case); in 1 patient, there was stable sinus tachycardia; and in 2 patients, who had chronic atrial fibrillation, there was an increase in ventricular rate. A total of 23 episodes of presyncope were documented in 8 patients (23%): no rhythm variation or mild tachycardia in 12 cases, paroxysmal atrial fibrillation or atrial tachycardia in 10 cases, and sustained ventricular tachycardia in 1 case. No patient died during the study period nor suffered from injury attributable to syncopal relapse. CONCLUSIONS: The patients with unexplained syncope, structural heart disease, and negative electrophysiologic study had a favorable medium-term outcome with no case of death and a low recurrence rate of syncope without related injury. The mechanism of syncope was heterogeneous, and ventricular tachyarrhythmia was unlikely.