Francesca Perego

Short- and long-term prognosis of syncope, risk factors, and role of hospital admission : results from the STePS (Short-Term Prognosis of Syncope) study

OBJECTIVE We sought to assess short- and long-term prognosis of syncope and associated risk factors. BACKGROUND Syncope is a common clinical event, but our knowledge of its short-term outcome is largely incomplete. Further, it is unknown whether hospital admission might positively affect a patients syncope prognosis. METHODS We screened 2,775 consecutive subjects who presented for syncope at 4 emergency departments between January and July 2004. Short- and long-term severe outcomes (i.e., death and major therapeutic procedures) and related risk factors were compared in all enrolled patients arrayed according to hospital admission or discharge. RESULTS A total of 676 subjects were included in the study. Forty-one subjects (6.1%) experienced severe outcomes (5 deaths, 0.7%; 36 major therapeutic procedures, 5.4%) in the 10 days after presentation. An abnormal electrocardiogram, concomitant trauma, absence of symptoms of impending syncope, and male gender were associated with short-term unfavorable outcomes. Long-term severe outcomes were 9.3% (40 deaths, 6.0%; 22 major therapeutic procedures, 3.3%), and their occurrence was correlated with an age >65 years, history of neoplasms, cerebrovascular diseases, structural heart diseases, and ventricular arrhythmias. Short-term major therapeutic procedures were more common (p < 0.05) in subjects who had been admitted to hospital (13.3%) than in discharged (1.6%), whereas mortality was similar. One-year mortality was greater (p < 0.05) in admitted (14.7%) than in discharged (1.8%) patients. CONCLUSIONS Risk factors for short- and long-term adverse outcomes after syncope differed. Hospital admission favorably influenced syncope short term prognosis. Instead, 1-year mortality was unaffected by hospital admission and related to comorbidity.

Clinical ResearchHeart Rhythm DisorderShort- and Long-Term Prognosis of Syncope, Risk Factors, and Role of Hospital Admission: Results From the STePS (Short-Term Prognosis of Syncope) Study

OBJECTIVE We sought to assess short- and long-term prognosis of syncope and associated risk factors. BACKGROUND Syncope is a common clinical event, but our knowledge of its short-term outcome is largely incomplete. Further, it is unknown whether hospital admission might positively affect a patients syncope prognosis. METHODS We screened 2,775 consecutive subjects who presented for syncope at 4 emergency departments between January and July 2004. Short- and long-term severe outcomes (i.e., death and major therapeutic procedures) and related risk factors were compared in all enrolled patients arrayed according to hospital admission or discharge. RESULTS A total of 676 subjects were included in the study. Forty-one subjects (6.1%) experienced severe outcomes (5 deaths, 0.7%; 36 major therapeutic procedures, 5.4%) in the 10 days after presentation. An abnormal electrocardiogram, concomitant trauma, absence of symptoms of impending syncope, and male gender were associated with short-term unfavorable outcomes. Long-term severe outcomes were 9.3% (40 deaths, 6.0%; 22 major therapeutic procedures, 3.3%), and their occurrence was correlated with an age >65 years, history of neoplasms, cerebrovascular diseases, structural heart diseases, and ventricular arrhythmias. Short-term major therapeutic procedures were more common (p < 0.05) in subjects who had been admitted to hospital (13.3%) than in discharged (1.6%), whereas mortality was similar. One-year mortality was greater (p < 0.05) in admitted (14.7%) than in discharged (1.8%) patients. CONCLUSIONS Risk factors for short- and long-term adverse outcomes after syncope differed. Hospital admission favorably influenced syncope short term prognosis. Instead, 1-year mortality was unaffected by hospital admission and related to comorbidity.

Early Abnormalities of Vascular and Cardiac Autonomic Control in Parkinson’s Disease Without Orthostatic Hypotension

Cardiac autonomic abnormalities have been described in Parkinson’s disease. Little is known about possible alterations of vascular sympathetic regulatory activity in patients without orthostatic hypotension or symptoms of orthostatic intolerance. Nineteen patients with Parkinson’s disease without orthostatic hypotension (PD), 21 with orthostatic hypotension (PDOH), and 20 healthy controls underwent ECG, beat-to-beat arterial pressure, and respiration recordings while recumbent and during a 75° head-up tilt. Spectrum analysis of RR interval and systolic arterial pressure (SAP) variability provided indices of cardiac sympathovagal interaction (low frequency [LF]/high frequency [HF]) to the sinoatrial node and sympathetic vasomotor control (LFSAP). Arterial baroreceptor mechanisms were assessed by the spontaneous sequences technique and bivariate spectrum analysis (&agr; index). Plasma catecholamines provided the neurohormonal profile. At rest, hemodynamics and spectral markers of autonomic function were similar in PD and control subjects. Norepinephrine was lower in PD and PDOH than in control subjects. In PDOH, SAP was higher, whereas LF/HF ratio and LFSAP were lower compared with control subjects. During tilt, SAP was unchanged in PD; however, similar to PDOH, the increase of heart rate, LF/HF ratio, and LFSAP was blunted compared with control subjects. Baroreflex indices were unmodified in PD and PDOH compared with control subjects. Initial alterations in both cardiac and vascular sympathetic modulatory activity were found in PD and revealed by a gravitational stimulus. Prompt recognition of sympathetic abnormalities might result in earlier therapeutic intervention, reduced orthostatic intolerance, and increased quality of life.

Peculiar HLA polymorphisms in Italian patients with primary biliary cirrhosis.

BACKGROUND/AIMS Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease of unknown etiology with a highly variable progression rate and prevalence among different geographical areas. Data concerning human leukocyte antigen (HLA) polymorphisms in PBC come from a limited number of geographical areas, from which the association with the HLA-DRB1*08 allele has been consistently reported. METHODS To investigate whether HLA polymorphisms contribute toward disease susceptibility, we compared 186 well-defined Italian PBC patients with 558 healthy subjects matched by age, gender and geographical area (Northern, Central and Southern Italy). Patients and controls were HLA typed at low resolution by PCR-sequence specific oligonucleotides for the loci A and B; HLA-DRB1 alleles were typed by reverse line blot assay of PCR-amplified DNA. RESULTS HLA-DRB1*11 was associated with a markedly reduced risk of developing PBC (OR: 0.3; 95% CI: 0.2-0.5). No association was found with HLA-DRB1*08. The B*15 (2.5; 1.3-4.6), B*41 (12.0; 2.7-72.1), B*55 (2.9; 1.1-7.5) and B*58 alleles (6.8; 1.1-46.3) were more frequent in PBC. The frequency of HLA polymorphisms was similar in PBC patients with progressive or non-progressive disease, and in those with or without anti-mitochondrial antibodies. CONCLUSIONS Our data on a large series of Italian patients suggest that PBC may have a peculiar genetic background in the Mediterranean area.

San Francisco Syncope Rule, Osservatorio Epidemiologico sulla Sincope nel Lazio risk score, and clinical judgment in the assessment of short-term outcome of syncope.

OBJECTIVE The study aimed to compare the efficacy of the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score, San Francisco Syncope Rule, and clinical judgment in assessing the short-term prognosis of syncope. METHODS We studied 488 patients consecutively seen for syncope at the emergency department of 2 general hospitals between January and July 2004. Sensitivity, specificity, predictive values, and likelihood ratios for short-term (within 10 days) severe outcomes were computed for each decision rule and clinical judgment. Severe outcomes comprised death, major therapeutic procedures, and early readmission to hospital. RESULTS Clinical judgment had a sensitivity of 77%, a specificity of 69%, and would have admitted less patients (34%, P < .05 vs decision rules). The OESIL risk score was characterized by a sensitivity of 88% and a specificity of 60% (admission 43%). San Francisco Syncope Rule sensitivity was 81% and specificity was 63% (admission 40%). According to both clinical rules, no discharged patient would have died. With combined OESIL risk score and clinical judgment, the probability of adverse events was 0.7% for patients with both low risk scores, whereas that for both high risk scores was roughly 16%. CONCLUSION Because of a relatively low sensitivity, both risk scores were partially lacking in recognizing patients with short-term high-risk syncope. However, the application of the decision rules would have identified all patients who subsequently died, and OESIL risk score and clinical judgment combined seem to improve the decision-making process concerning the identification of high-risk patients who deserve admission.

Effects of high-amount–high-intensity exercise on in vivo platelet activation: Modulation by lipid peroxidation and AGE/RAGE axis

Physical activity is associated with cardiovascular risk reduction, but the effects of exercise on platelet activation remain controversial. We investigated the effects of regular high-amount, high intensity aerobic exercise on in vivo thromboxane (TX)-dependent platelet activation and plasma levels of platelet-derived proteins, CD40L and P-selectin, and whether platelet variables changes may be related to changes in high-density lipoprotein (HDL) and in the extent of oxidative stress and oxidative stress-related inflammation, as reflected by urinary isoprostane excretion and endogenous soluble receptor for advanced glycation end-products (esRAGE), respectively. Urinary excretion of 11-dehydro-TXB₂ and 8-iso-prostaglandin (PG)F(2α) and plasma levels of P-selectin, CD40L and esRAGE were measured before and after a eight-week standardised aerobic high-amount-high-intensity training program in 22 sedentary subjects with low-to-intermediate risk. Exercise training had a clear beneficial effect on HDL cholesterol (+10%, p=0.027) and triglyceride (-27%, p=0.008) concentration. In addition, a significant (p<0.0001) decrease in urinary 11-dehydro-TXB₂ (26%), 8-iso-PGF(2α) (21%), plasma P-selectin (27%), CD40L (35%) and a 61% increase in esRAGE were observed. Multiple regression analysis revealed that urinary 8-iso-PGF(2α) [beta=0.33, SEM=0.116, p=0.027] and esRAGE (beta=-0.30, SEM=31.3, p=0.046) were the only significant predictors of urinary 11-dehydro-TXB₂ excretion rate over the training period. In conclusion, regular high-amount-high-intensity exercise training has broad beneficial effects on platelet activation markers, paralleled and possibly associated with changes in the lipoprotein profile and in markers of lipid peroxidation and AGE/RAGE axis. Our findings may help explaining why a similar amount of exercise exerts significant benefits in preventing cardiovascular events.

Influence of climate on emergency department visits for syncope: role of air temperature variability.

Background Syncope is a clinical event characterized by a transient loss of consciousness, estimated to affect 6.2/1000 person-years, resulting in remarkable health care and social costs. Human pathophysiology suggests that heat may promote syncope during standing. We tested the hypothesis that the increase of air temperatures from January to July would be accompanied by an increased rate of syncope resulting in a higher frequency of Emergency Department (ED) visits. We also evaluated the role of maximal temperature variability in affecting ED visits for syncope. Methodology/Principal Findings We included 770 of 2775 consecutive subjects who were seen for syncope at four EDs between January and July 2004. This period was subdivided into three epochs of similar length: 23 January–31 March, 1 April–31 May and 1 June–31 July. Spectral techniques were used to analyze oscillatory components of day by day maximal temperature and syncope variability and assess their linear relationship. There was no correlation between daily maximum temperatures and number of syncope. ED visits for syncope were lower in June and July when maximal temperature variability declined although the maximal temperatures themselves were higher. Frequency analysis of day by day maximal temperature variability showed a major non-random fluctuation characterized by a ∼23-day period and two minor oscillations with ∼3- and ∼7-day periods. This latter oscillation was correlated with a similar ∼7-day fluctuation in ED visits for syncope. Conclusions/Significance We conclude that ED visits for syncope were not predicted by daily maximal temperature but were associated with increased temperature variability. A ∼7-day rhythm characterized both maximal temperatures and ED visits for syncope variability suggesting that climate changes may have a significant effect on the mode of syncope occurrence.

Baroreflex Regulation of Sympathetic Nerve Activity in Patients With Vasovagal Syncope

To the Editor: In their study, “Dysfunctional Baroreflex Regulation of Sympathetic Nerve Activity in Patients With Vasovagal Syncope,” Bechir et al1 implied a unilateral causal relationship between reduction of arterial baroreflex control of heart rate and increase of muscle sympathetic nerve activity (MSNA) in patients with syncope. The authors concluded that dysfunctional baroreflex regulation of sympathetic activity provides “new insights into the mechanisms of vasovagal syncope…” We have two comments. Baroreflex function can be depressed by suprabulbar central influences and also by vagal, somatic, or sympathetic2 afferents. …

Why meta-analyses on the same topic lead to different conclusions?

Berger [1] ‘‘There was no significant reduction for myocardial infarction, stroke, ischemic stroke, or allcause mortality.’’ (all-cause mortality: RR 0.94, 95 % CI 0.89–1.00, p = 0.07). Raju [2] ‘‘Aspirin prevents deaths, myocardial infarction...’’ (deaths: RR 0.94; 95 % CI, 0.88–1.00 p = 0.05). Seshasai [3] ‘‘Modest, but not significant, reductions were observed for total CHD..., total nonvascular mortality..., and all-cause mortality...’’ (all-cause mortality: OR 0.94; 95 % CI, 0.88–1.00).

Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction

Background Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes. Objective Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation. Methods Twenty-three HAE patients (6 males, mean age 47.5±11.4 years) during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years) were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10’) and 75-degrees-head-up tilt (10’). C1-INH, C4, cleaved high molecular weight kininogen (cHK) were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF) and high-(HF) frequency components, markers of sympathetic and vagal modulation respectively. Results HAE patients showed higher mean systolic arterial pressure (SAP) than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu) increased significantly with tilt in both groups, LF/HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5±89.6pg/ml, p = 0.05). Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01). Conclusions Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.