Carlo Menozzi

Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome A Prospective Evaluation of 52 Families

BackgroundThe ECG pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and ResultsSixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). ConclusionsAt variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

Diagnostic value of history in patients with syncope with or without heart disease

OBJECTIVES We sought to establish what historical findings are predictive of the cause of syncope. BACKGROUND The clinical features of the various types of syncope have not been systematically investigated. METHODS Three hundred forty-one patients with syncope were prospectively evaluated. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. RESULTS A cardiac cause of syncope was established in 23% of the patients, a neurally mediated cause in 58% and a neurologic or psychiatric cause in 1%, and in the remaining 18%, the cause of syncope remained unexplained. In a preliminary analysis including age, gender and the presence of suspected or certain heart disease after the initial evaluation, only heart disease was an independent predictor of a cardiac cause of syncope (odds ratio 16, p = 0.00001), with a sensitivity of 95% and a specificity of 45%. In contrast, the absence of heart disease allowed us to exclude a cardiac cause of syncope in 97% of the patients. In patients with certain or suspected heart disease, the most specific predictors of a cardiac cause were syncope in the supine position or during effort, blurred vision and convulsive syncope. Significant and specific predictors of a neurally mediated cause were time between the first and last syncopal episode >4 years, abdominal discomfort before the loss of consciousness and nausea and diaphoresis during the recovery phase. In the patients without heart disease, palpitation was the only significant predictor of a cardiac cause. CONCLUSIONS The presence of suspected or certain heart disease after the initial evaluation is a strong predictor of a cardiac cause of syncope. A few historical findings are useful to predict cardiac and neurally mediated syncope in patients with and without heart disease.

Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients With Heart Failure and Chronic Atrial Fibrillation A Randomized, Controlled Study

BACKGROUND Uncontrolled studies have suggested that atrioventricular junction ablation and pacemaker implantation have beneficial effects on quality of life in patients with chronic atrial fibrillation (AF). METHODS AND RESULTS We performed a multicenter, controlled, randomized, 12-month evaluation of the clinical effects of atrioventricular junction ablation and VVIR pacemaker (Abl+Pm) versus pharmacological (drug) treatment in 66 patients with chronic (lasting >6 months) AF who had clinically manifest heart failure and heart rate >90 bpm on 3 standard ECGs recorded at rest during stable clinical conditions on different days. Before completion of the study, withdrawals occurred in 8 patients of the drug group and in 4 patients of the Abl+Pm group. At the end of the 12 months, the 28 Abl+Pm patients who completed the study showed lower scores in palpitations (-78%; P=0.000) and effort dyspnea (-22%; P=0.05) than the 26 of the drug group. Lower scores, although not significant, were also observed for exercise intolerance (-20%), easy fatigue (-17%), chest discomfort (-50%), Living with Heart Failure Questionnaire (-14%), New York Heart Association functional classification (-4%), and Activity scale (-12%). The intrapatient comparison between enrollment and month 12 showed that in the Abl+Pm group, all variables except easy fatigue improved significantly from 14% to 82%. However, because an improvement was also observed in the drug group, the difference between the 2 groups was significant only for palpitations (P=0.000), effort dyspnea (P=0.01), exercise intolerance (P=0.005), easy fatigue (P=0.02), and chest discomfort (P=0.02). Cardiac performance, evaluated by means of standard echocardiogram and exercise test, did not differ significantly between the 2 groups and remained stable over time. CONCLUSIONS In patients with heart failure and chronic AF, Abl+Pm treatment is effective and superior to drug therapy in controlling symptoms, although its efficacy appears to be less than that observed in uncontrolled studies because some improvement can also be expected in medically treated patients. Cardiac performance is not modified by the treatment.

Dual-Chamber Pacing in the Treatment of Neurally Mediated Tilt-Positive Cardioinhibitory Syncope Pacemaker Versus No Therapy: A Multicenter Randomized Study

BACKGROUND-This study was performed to compare implantation of a DDI pacemaker with rate hysteresis with no implant in respect to syncopal recurrences in patients with severe cardioinhibitory tilt-positive neurally mediated syncope. METHODS AND RESULTS-Forty-two patients from 18 European centers were randomized to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19 patients) or no pacemaker (23 patients). Inclusion criteria were >/=3 syncopes over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope International Study types 2A and 2B) response to tilt testing. The median number of previous syncopal episodes was 6; asystolic response to tilt testing was present in 36 patients (86%) (mean asystole, 13.9+/-10.2 seconds). All patients were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean, 3.7+/-2.2). One patient (5%) in the pacemaker arm experienced recurrence of syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In the no-pacemaker arm, the median time to first syncopal recurrence was 5 months, with a rate of 0.44 per year. On repeated tilt testing performed within 15 days after enrollment, positive responses were observed in 59% of patients with pacemakers and in 61% of patients without pacemakers (P=NS). CONCLUSIONS-In a limited, select group of patients with tilt-positive cardioinhibitory syncope, DDI pacing with hysteresis reduced the likelihood of syncope. The benefit of the therapy was maintained over the long term. Even in untreated patients, the syncopal recurrence burden was low. A negative result of tilt testing was not a useful means to evaluate therapy efficacy.

Assessment of Atrioventricular Junction Ablation and DDDR Mode-Switching Pacemaker Versus Pharmacological Treatment in Patients With Severely Symptomatic Paroxysmal Atrial Fibrillation A Randomized Controlled Study

BACKGROUND The purpose of the study was to evaluate the effect of AV junction ablation and pacemaker implantation on quality of life and specific symptoms in patients with paroxysmal atrial fibrillation (AF) not controlled by drugs. METHODS AND RESULTS We performed a multicenter, randomized, 6-month evaluation of the clinical effects of AV junction ablation and DDDR mode-switching pacemaker (Abl+Pm) versus pharmacological treatment in 43 patients with intolerable, recurrent paroxysmal AF of three or more episodes in the previous 6 months not controlled with three or more antiarrhythmic drugs. Before completion of the study, 3 patients in the drug group withdrew because of the severity of their symptoms and 1 patient assigned to the Abl+Pm group in whom the ablation procedure failed. At the end of the 6 months, the 21 patients of the Abl+Pm group who completed the study showed, in comparison with the 18 of the drug group, lower scores in the Living with Heart Failure Questionnaire (-51%, P=.0006), palpitations (-71%, P=.0000), effort dyspnea (-36%, P=.04), exercise intolerance score (-46%, P=.001), and easy fatigue (-51%, P=.02). The scores for rest dyspnea, chest discomfort, and NYHA functional classification were also lower (-56%, -50%, and -17%, respectively) in the Abl+Pm group, although not significantly. At the end of the study, palpitations were no longer present in 81% of the Abl+Pm group and in 11% of the drug group (P=.0000). AF was documented in 31 of 122 visits (25%) in the Abl+Pm group and in 9 of 107 examinations (8%) in the drug group (P=.0005); chronic AF developed in 5 (24%) and 0 (0%) in the two groups, respectively (P=.04). CONCLUSIONS In patients with paroxysmal AF not controlled by pharmacological therapy, Abl+Pm treatment is highly effective and superior to drug therapy in controlling symptoms and improving quality of life. The discontinuation of drug therapy exposes patients to further recurrences of paroxysmal AF and the risk of developing permanent AF.

Value of head-up tilt testing potentiated with sublingual nitroglycerin to assess the origin of unexplained syncope

This study was undertaken to assess the value of sublingual nitroglycerin administration during upright tilt as a simple practical test for the diagnosis of vasovagal syncope. To this purpose, 235 patients with syncope of unknown origin and no evidence of organic heart disease (110 men, mean age 52 +/- 20 years) and 35 asymptomatic control subjects underwent head-up tilt testing with nitroglycerin challenge. Patients and subjects were tilted at 60 degrees for 45 + 20 minutes; the initial 45 minutes were without medication and the final 20 minutes after 300 micrograms of sublingual nitroglycerin. During the drug-free phase of the test, 59 patients (25%) and no controls had a positive response. After drug administration, a positive response (syncope in association with sudden hypotension and bradycardia) occurred in 60 patients (26%) and in 2 controls (6%), whereas an exaggerated or false-positive response (minor or different symptoms in association with slowly increasing hypotension alone) was observed in 33 patients (14%) and in 5 controls (14%). We conclude that the sublingual nitroglycerin head-up tilt test is a useful tool to unmask the vasovagal origin of unexplained syncope in patients without organic heart disease. The addition of nitroglycerin to upright tilt allows the positive rate of passive tilting to be doubled (51% vs 25%) while maintaining a high specificity (94% vs 100%).

Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score

Objective: To develop, in patients referred for syncope to an emergency department (ED), a diagnostic score to identify those patients likely to have a cardiac cause. Design: Prospective cohort study. Setting: ED of 14 general hospitals. Patients: 516 consecutive patients with unexplained syncope. Interventions: Subjects underwent a diagnostic evaluation on adherence to Guidelines of the European Society of Cardiology. The clinical features of syncope were analysed using a standard 52-item form. In a validation cohort of 260 patients the predictive value of symptoms/signs was evaluated, a point score was developed and then validated in a cohort of 256 other patients. Main outcome measurements: Diagnosis of cardiac syncope, mortality. Results: Abnormal ECG and/or heart disease, palpitations before syncope, syncope during effort or in supine position, absence of autonomic prodromes and absence of predisposing and/or precipitating factors were found to be predictors of cardiac syncope. To each variable a score from +4 to –1 was assigned to the magnitude of regression coefficient. A score ⩾3 identified cardiac syncope with a sensitivity of 95%/92% and a specificity of 61%/69% in the derivation and validation cohorts, respectively. During follow-up (mean (SD) 614 (73) days) patients with score ⩾3 had a higher total mortality than patients with a score <3 both in the derivation (17% vs 3%; p<0.001) and in the validation cohort (21% vs 2%; p<0.001). Conclusions: A simple score derived from clinical history can be usefully employed for the triage and management of patients with syncope in an ED.

Influence of atrioventricular junction radiofrequency ablation in patients with chronic atrial fibrillation and flutter on quality of life and cardiac performance

The purpose of this study was to evaluate the effects of atrioventricular junction radiofrequency ablation on the quality of life, exercise performance, and echocardiographic parameters in 23 patients with chronic, severely symptomatic, drug-refractory atrial fibrillation or flutter. Initially, patients were randomized to receive ablation plus pacemaker therapy (n = 12) or pacemaker therapy alone (n = 11). After 15 days, palpitations decreased by 92% and 37% (p = 0.004), rest dyspnea by 79% and 40% (p = NS), effort dyspnea by 65% and 30% (p = 0.03), exercise intolerance by 54% and 17% (p = 0.005), and asthenia by 67% and 31% (p = 0.02) in the 2 groups, respectively. At the end of this short-term study, control patients also underwent ablation therapy, and a 3-month intrapatient follow-up study was performed in 22 patients. New York Heart Association functional class > or = 3 was present in 14 patients (64%) before, but in only 3 patients (14%) after ablation therapy (p = 0.002); specific activity scale functional class > or = 3 was present in 9 patients (41%) before, but in only 5 (23%) after ablation therapy (p = NS). Exercise duration during standardized stress testing increased by a mean of 63 +/- 93 seconds (15% increase) (p = 0.001). In the 9 patients with depressed left ventricular systolic function, echocardiographic fractional shortening increased by 34% (from 23 +/- 5% to 31 +/- 9%) (p = 0.003). In the remaining 13 patients with normal systolic function, fractional shortening decreased by 10% (from 40 +/- 5% to 36 +/- 6%) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole Third International Study on Syncope of Uncertain Etiology (ISSUE-3): A Randomized Trial

Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P =0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: . Unique identifier: [NCT00359203][1]. # Clinical Perspective {#article-title-19} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00359203&atom=%2Fcirculationaha%2F125%2F21%2F2566.atom

A controlled trial of acute and long-term medical therapy in tilt-induced neurolly mediated syncope

To study the efficacy of medical treatment for preventing syncopal recurrences in patients affected by tilt-induced neurally mediated syncope, a randomized placebo-treatment prospective study was performed in 30 patients (10 men and 20 women, mean age 42 +/- 21 years) who had syncope reproduced in 2 consecutive head-up tilt-table tests without pharmacologic intervention (n = 20) or during isoproterenol infusion (n = 10). Patients were randomly assigned to 2 groups: 15 to placebo, and 15 to drug therapy (determined on the basis of serial pharmacologic tilting tests). Therapy was either atenolol (n = 7), dihydroergotamine (n = 2), domperidone (n = 2), cafedrine (n = 1), or elastic compression stockings, alone or in association with drugs (n = 3). During a mean of 10 +/- 7 months of follow-up, syncope recurred in 3 patients (20%) in the treatment group and in 4 (27%) in the placebo group; actuarial rates of absence of syncopal recurrences after 20 months were 70 and 67%, respectively. Thus, the outcome of either treated or untreated patients was favorable (with a low recurrence rate of syncope), and the usefulness of tilting-guided medical therapy remains uncertain.