Assessment of systolic ejection time as a hemodynamic marker of incipient bradycardic vasovagal syncope. A pilot study.

BACKGROUND: Detection of markers of incipient syncope in patients with vasovagal syncope (VVS), without prodromal symptom, is still an open issue. The aim of this study was to assess the behavior of heart rate (HR) and ejection time, expressed as the percentage of the corresponding cardiac cycle (ET%), in patients with bradycardic VVS with a view to providing an alarm before the event. METHODS: In 33 patients with syncope and positive tilt testing and in 33 control patients, we collected beat-to-beat data on HR, ET%, stroke volume (SV), and blood pressure (BP). The trends of HR and ET% were analyzed. A set of combined changes of HR and ET% were tested in order to select the most appropriate algorithm for detecting the incipient syncope within the 3 minutes preceding the event. RESULTS: In patients with positive tilt testing, BP significantly decreased at 3 minutes before and at the time of syncope (P < 0.0001). HR slowly rose at 3 minutes before syncope and then suddenly decreased at the time of syncope (P < 0.0001). The correlation between SV and ET% was r = 0.79 (P < 0.0001). SV and ET% significantly decreased throughout tilt testing (P < 0.0001). The selected setting for the algorithm provided sensitivity of 97% and specificity of 73%. The theoretical alarm was generated at least 9 and 5 seconds before syncope, respectively, in 76% and 85% of the subjects. CONCLUSION: The combined trends in HR and ET% may provide a marker of incipient bradycardic VVS in the majority of patients.

Simultaneous occurrence of two independent vagal reflexes: a possible cause of vagal sudden death.

A vagal origin of sudden death has been hypothesised in humans, but it has not yet been clearly demonstrated. Two vagal reflexes have been widely investigated: the diving reflex and the fear-induced central reaction, which are responsible for diving bradycardia and alarm bradycardia, respectively. The latter occurs in humans mainly in the context of emotional presyncope/syncope. A simultaneous occurrence of these two vagal reflexes has been observed in animals that are threatened while diving, and heart rates (HR) as low as two to six beats/min have been reported. In experiments carried out in rats, a high percentage of animals that were stressed before immersion in water died suddenly due to progressive slowing of HR; autopsy revealed no signs of drowning. No animals died if they had not been previously stressed. These data show that vagal sudden death can occur when the vagal cardiac fibres are synergically stimulated by two independent reflexes. In humans, it has been reported that in 10-15% of people who die after falling into water, autopsy reveals little or no water in the lungs. These sudden deaths could be due to vagal overactivity. The development of an adequate laboratory model may improve knowledge of the pathophysiology of this type of vagal sudden death and of its prevention.

Diving bradycardia: a mechanism of defence against hypoxic damage.

A feature of all air-breathing vertebrates, diving bradycardia is triggered by apnoea and accentuated by immersion of the face or whole body in cold water. Very little is known about the afferents of diving bradycardia, whereas the efferent part of the reflex circuit is constituted by the cardiac vagal fibres. Diving bradycardia is associated with vasoconstriction of selected vascular beds and a reduction in cardiac output. The diving response appears to be more pronounced in mammals than in birds. In humans, the bradycardic response to diving varies greatly from person to person; the reduction in heart rate generally ranges from 15 to 40%, but a small proportion of healthy individuals can develop bradycardia below 20 beats/min. During prolonged dives, bradycardia becomes more pronounced because of activation of the peripheral chemoreceptors by a reduction in the arterial partial pressure of oxygen (O2), responsible for slowing of heart rate. The vasoconstriction is associated with a redistribution of the blood flow, which saves O2 for the O2-sensitive organs, such as the heart and brain. The results of several investigations carried out both in animals and in humans show that the diving response has an O2-conserving effect, both during exercise and at rest, thus lengthening the time to the onset of serious hypoxic damage. The diving response can therefore be regarded as an important defence mechanism for the organism.

Systolic heart failure: should we care about electrical, mechanical or electromechanical dyssynchrony?

Prolonged QRS duration is electrocardiographic evidence of electrical dyssynchrony and is associated with a higher incidence of cardiac events and mortality. The study by Cho et al. (167 patients were followed up for 33.4 +/- 19.9 months) shows that mechanical dyssynchrony has an additional value over QRS duration in predicting cardiac events in patients with systolic heart failure. The dyssynchrony was assessed through tissue Doppler imaging - a temporal difference between the septal to lateral wall (Ts-1) of 65 ms or more defined the mechanical dyssynchrony. In multivariate Cox proportional hazard analysis, both QRS duration (hazard ratio [HR]: 1.85; p = 0.032) and Ts-1 (HR: 2.35; p = 0.002) were independent predictors of cardiac events. Those with both electrical and mechanical dyssynchrony had a HR of 3.98 (95% CI: 2.02-7.86; p < 0.001) when compared with those with a normal QRS duration and absence of mechanical dyssynchrony. Combining the information provided by QRS duration with mechanical dyssynchrony through Ts-1 is clinically relevant to stratifying the risk of hospitalization or death in systolic heart failure patients. However, these data do not support the use of mechanical dyssynchrony to select patients for cardiac resynchronization therapy, nor to predict response to this therapy. This was not assessed by the study.

Cardiac resynchronization therapy: back to ECG?

In recent years, considerable effort has been devoted to improving patient selection and the programming of cardiac resynchronization therapy (CRT). Mechanical dyssynchrony has been investigated through echocardiography and the reliability of ECG in selecting patients has been criticized and doubt has been cast on its role. Up to now, patient selection for CRT has relied upon the criteria of a prolonged QRS, evidence of the electrical impairment of the conduction system. Can we get more information from ECG morphology? Can it provide any marker for selecting candidates to CRT? Can we obtain useful information from the paced ECG morphology by analysis of fusion beats? Can we use ECG to optimize biventricular or single-site left ventricular pacing programming? The present review provides a critical analysis of the criteria for patient selection and the methods for optimal device setting, all based on 12-lead ECG morphology.

[Upstream therapy of atrial fibrillation in patients with heart failure]. / Il trattamento "upstream" della fibrillazione atriale nei pazienti con scompenso cardiaco.

Experimental data, results of retrospective studies and of small randomized trials suggest an efficacy of upstream therapy of atrial fibrillation (AF) with angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers, statins and n-3 polyunsaturated fatty acids (PUFA). These drugs seem to act by antagonizing the renin-angiotensin system, inflammation, oxidative stress and endothelial dysfunction, all factors that play an important role in the genesis of the substrate of AF and atrial remodeling. However, the recent Italian GISSI-AF study, which is the first large, multicenter, prospective and randomized trial (valsartan vs placebo) dealing with upstream therapy in the secondary prevention of AF, offered negative results. A trend toward a lower incidence of AF recurrence was apparent only in the valsartan group in patients presenting with heart failure, even if statistical significance was not reached. On the basis of these recent data, we analyzed the contributions offered by the literature on upstream therapy of AF in patients with heart failure in order to evaluate a possible use of this treatment in clinical practice. Six retrospective studies dealing with the primary prevention of AF (3 with ACE-inhibitors/angiotensin receptor blockers and 3 with statins) have been published; in these studies, upstream therapy was constantly effective. A recent meta-analysis, which included trials dealing with the primary prevention of AF with ACE-inhibitors/angiotensin receptor blockers, showed that patients with heart failure benefited the most. Up to now, the contributions on upstream therapy in the secondary prevention of AF in patients with heart failure are very few. These results are still not enough to recommend the clinical use of upstream therapy of AF in patients with heart failure because of the retrospective design of the studies. However, it emerges a background to plan a large-scale prospective, randomized trial on upstream therapy in the primary prevention of AF in patients with heart failure.

Treatment of persistent sinus bradycardia with intermittent symptoms: are guidelines clear?

There is uncertainty in the aetiology of syncope in subjects with persistent sinus bradycardia (SB) (sick sinus syndrome). The results of pathophysiological studies suggest a reflex origin of syncope in the vast majority of subjects with SB. From a nosological point of view, 'syndrome' is defined as the association of signs and symptoms that have a pathophysiological correlation. Since in most cases the causal relationship between syncope and persistent SB appears very weak, 'reflex syncope with associated SB' appears to be the most appropriate diagnosis.

Do subjects with vasovagal syncope have subtle haemodynamic alterations during orthostatic stress?

AIMS: There are conflicting reports on the presence of subtle haemodynamic alterations during orthostatic stress in subjects with vasovagal syncope (VVS). The aim of the present study was to investigate whether young/middle-aged subjects with VVS show abnormal responses to orthostatic stress. METHODS AND RESULTS: Four groups of subjects underwent tilt testing (TT) during the passive phase and, if negative, after nitroglycerin administration: Group I, 20 subjects with a history of syncope and positive passive TT; Group II, 23 subjects with a history of syncope and TT positive after nitroglycerin; Group III, 23 subjects with a history of syncope and negative TT; and Group IV, 20 normal control subjects. Heart rate, systolic, diastolic, and mean blood pressure, stroke volume, cardiac output, and total peripheral resistance were computed from pressure pulsations (Modelflow). The demographic data and the values of the haemodynamic variables in the supine position did not differ significantly among the four groups. The per cent changes in these variables did not differ significantly among the four groups after 2 and 5 min of TT and among Groups II, III, and IV, 2 min after nitroglycerin administration. CONCLUSION: Young/middle-aged subjects with VVS have a normal measured haemodynamic response to orthostatic stress; therefore, the vasovagal reflex is not secondary to an impairment of the primary vasoconstrictive mechanism.

Fusion beat in patients with heart failure treated with left ventricular pacing: may ECG morphology relate to mechanical synchrony? A pilot study.

BACKGROUND: Electrical fusion between left ventricular pacing and spontaneous right ventricular activation is considered the key to resynchronisation in sinus rhythm patients treated with single-site left ventricular pacing. AIM: Use of QRS morphology to optimize device programming in patients with heart failure (HF), sinus rhythm (SR), left bundle branch block (LBBB), treated with single-site left ventricular pacing. METHODS AND RESULTS: We defined the "fusion band" (FB) as the range of AV intervals within which surface ECG showed an intermediate morphology between the native LBBB and the fully paced right bundle branch block patterns.Twenty-four patients were enrolled. Echo-derived parameters were collected in the FB and compared with the basal LBBB condition. Velocity time integral and ejection time did not improve significantly. Diastolic filling time, ejection fraction and myocardial performance index showed a statistically significant improvement in the FB. Interventricular delay and mitral regurgitation progressively and significantly decreased as AV delay shortened in the FB. The tissue Doppler asynchrony index (Ts-SD-12-ejection) showed a non significant decreasing trend in the FB. The indications provided by the tested parameters were mostly concordant in that part of the FB corresponding to the shortest AV intervals. CONCLUSION: Using ECG criteria based on the FB may constitute an attractive option for a safe, simple and rapid optimization of resynchronization therapy in patients with HF, SR and LBBB.

Current treatment of recurrent vasovagal syncope: between evidence-based therapy and common sense.

Vasovagal syncope is very frequent and benign and the vast majority of subjects do not need any specific treatment, but only reassurance and education. An unknown but small percentage of patients require specific treatment when syncope is very frequent or is responsible for major trauma. For these patients, there are some evidence-based therapies available and some first-line treatments appear to be established. The therapeutic choice mainly depends on the presence and duration of prodromal symptoms. In subjects aged < 70 years with well recognizable prodromes, the first-line treatment is counterpressure manoeuvres. In patients with no or minimal prodromes, but with tilt testing and carotid sinus massage (CSM) both positive, cardiac pacing appear to be the first-line therapy. However, an area of uncertainty remains, represented by patients with no or minimal prodromes and negative CSM. For these patients, appropriate treatment (drugs, tilt training, cardiac pacing, relaxation-based treatment) can be chosen by considering the clinical context, the risk of trauma and possible comorbidities, in addition to utilizing the little or controversial knowledge available, as well as common sense.

Successful treatment of electrical storm with oral quinidine in Brugada syndrome.

A patient implanted with a cardioverter-defibrillator for symptomatic Brugada syndrome was referred to our hospital 17 months later because of recurrent shocks due to ventricular fibrillation (VF). Isoprenaline was intravenously infused and prevented VF episodes, but VF recurred after every attempt of drug discontinuation. A total of 34 shocks were recorded over 25 days. Subsequently, we treated the patient with oral quinidine and the drug suppressed the electrical storm and prevented VF episodes during a follow-up period of 3 years. This case report, together with few others reported in the literature, suggests a role of oral quinidine in the treatment of electrical storm in Brugada syndrome.

The fusion band in V1: a simple ECG guide to optimal resynchronization? An echocardiographic case report.

BACKGROUND: Patients with left bundle branch block have a preserved right bundle branch conduction and the efficacy of left ventricular pacing could be explained with the fusion between artificial pulse delivered in the left lateral wall and the spontaneous right ventricular activation. Moreover, the efficacy of left ventricular pacing could be enhanced with an optimal timing between the spontaneous right ventricular activation and the left ventricular pulse. CASE PRESENTATION: We evaluated a patient (male, 47 yrs) with surgically corrected mitral regurgitation, sinus rhythm and left bundle branch block, heart failure (NYHA class III) despite medical therapy and low ejection fraction (25%): he was implanted with a biventricular device. We programmed ventricular pacing only through the left ventricular lead. We defined what we called electrocardiographic "fusion band" as follow: programming OFF the stimulator, we recorded the native electrocardiogram and measured, through the device, the intrinsic atrioventricular interval. Then, atrioventricular interval was progressively shortened by steps of 20 ms down to 100 ms. Twelve leads electrocardiogram was recorded at each step. The fusion band is the range of AV intervals at which surface electrocardiogram (mainly in V1 lead) presents an intermediate morphology between the native left bundle branch block (upper limit of the band) and the fully paced right bundle branch block (lower limit). The patient underwent echocardiographic examination at each atrioventricular interval chosen inside the fusion band. The following parameters were evaluated: ejection fraction, diastolic filling time, E wave deceleration time, aortic velocity time integral and myocardial performance index. All the echocardiographic parameters showed an improvement inside the fusion band, with a "plateau" behaviour. As the fusion band in this patient ranged from an atrioventricular delay of 200 ms to an atrioventricular delay of 120 ms, we chose an intermediate atrioventricular delay of 160 ms, presuming that this might guarantee the persistence of fusion even during any possible physiological (autonomic, effort) atrioventricular conduction variation. CONCLUSION: In this heart failure patient with left bundle branch block, tailoring of the atrioventricular interval resynchronized myocardial contraction with left ventricular pacing alone, utilizing a sensed right atrial activity and the surface electrocardiographic pattern.

Antiarrhythmic drugs in patients with recurrent atrial fibrillation: where are we?

In patients with recurrent atrial fibrillation (AF), the hallmark of treatment has long been the use of antiarrhythmic drugs. The following strategies are available: a) any antiarrhythmic treatment; b) out-of-hospital episodic treatment ("pill-in-the-pocket" approach); c) prophylactic antiarrhythmic therapy; and d) hybrid therapy. The following patients with recurrent AF should not undergo any antiarrhythmic therapy: after the first AF episode; patients with rare, hemodynamically well-tolerated and short-lasting (a few hours) AF episodes; patients with perioperative AF, without history of recurrent AF; patients with AF during acute myocardial infarction or other acute diseases, without history of recurrent AF; and "holiday heart" syndrome. In patients with infrequent AF episodes (< 1 per month) and hemodynamically well-tolerated, but long enough to require emergency room intervention or hospitalization, a good treatment might be the "pill-in-the-pocket" approach, consisting of a single-dose oral ingestion of flecainide or propafenone at the time and place of palpitation onset. A recent Italian study has shown that this treatment is effective and safe. When AF episodes are frequent and/or hemodynamically badly tolerated, the treatment of choice is the prophylactic therapy with antiarrhythmic drugs. When these drugs fail (ineffective or not tolerated) a non-pharmacological treatment or a hybrid therapy may be indicated.

Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach.

BACKGROUND: In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation. We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital. METHODS: We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated. Of these patients, 58 (22 percent) were excluded from the study because of treatment failure or side effects. Out-of-hospital self-administration of flecainide or propafenone--the "pill-in-the-pocket" approach--after the onset of heart palpitations was evaluated in the remaining 210 patients (mean age [+/-SD], 59+/-11 years). RESULTS: During a mean follow-up of 15+/-5 months, 165 patients (79 percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92 percent) were treated 36+/-93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94 percent); the time to resolution of symptoms was 113+/-84 minutes. Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients. The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode (P<0.001 for both comparisons). CONCLUSIONS: In a selected, risk-stratified population of patients with recurrent atrial fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate of compliance by patients, a low rate of adverse events, and a marked reduction in emergency room visits and hospital admissions.

Feasibility and safety of noninvasive pacemaker stress echocardiography with externally triggered stimulation.

The aim of this study was to assess the feasibility and safety of stress echocardiography by triggering an implanted pacemaker through an external stimulator. The implanted pacemaker was set in triggered mode with unipolar sensitivity of <2 mV. The external stimulator, connected to 2 skin electrodes, tracked the implanted pacemaker at increasing rates. Fifteen patients (mean age 65 +/- 8 years) with suspected coronary artery disease entered the study, and complete tests were performed in all patients. No adverse effects were reported. The method of externally triggered stimulation is feasible, safe, and allows a diagnosis in every patient with a pacemaker without additional cost.