Giorgio Costantino

Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior.

The neural regulation of circulatory function is mainly effected through the interplay of the sympathetic and vagal outflows. This interaction can be explored by assessing cardiovascular rhythmicity with appropriate spectral methodologies. Spectral analysis of cardiovascular signal variability, and in particular of RR period (heart rate variability, HRV), is a widely used procedure to investigate autonomic cardiovascular control and/or target function impairment. The oscillatory pattern which characterizes the spectral profile of heart rate and arterial pressure short-term variability consists of two major components, at low (LF, 0.04-0.15Hz) and high (HF, synchronous with respiratory rate) frequency, respectively, related to vasomotor and respiratory activity. With this procedure the state of sympathovagal balance modulating sinus node pacemaker activity can be quantified in a variety of physiological and pathophysiological conditions. Changes in sympathovagal balance can be often detected in basal conditions, however a reduced responsiveness to an excitatory stimulus is the most common feature that characterizes numerous pathophysiological states. Moreover the attenuation of an oscillatory pattern or its impaired responsiveness to a given stimulus can also reflect an altered target function and thus can furnish interesting prognostic markers. The dynamic assessment of these autonomic changes may provide crucial diagnostic, therapeutic and prognostic information, not only in relation to cardiovascular, but also non-cardiovascular disease. As linear methodologies fail to provide significant information in conditions of extremely reduced variability (e.g. strenuous exercise, heart failure) and in presence of rapid and transients changes or coactivation of the two branches of autonomic nervous system, the development of new non-linear approaches seems to provide a new perspective in investigating neural control of cardiovascular system.

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.

Syncope risk stratification tools vs clinical judgment: An individual patient data meta-analysis

BACKGROUND There have been several attempts to derive syncope prediction tools to guide clinician decision-making. However, they have not been largely adopted, possibly because of their lack of sensitivity and specificity. We sought to externally validate the existing tools and to compare them with clinical judgment, using an individual patient data meta-analysis approach. METHODS Electronic databases, bibliographies, and experts in the field were screened to find all prospective studies enrolling consecutive subjects presenting with syncope to the emergency department. Prediction tools and clinical judgment were applied to all patients in each dataset. Serious outcomes and death were considered separately during emergency department stay and at 10 and 30 days after presenting syncope. Pooled sensitivities, specificities, likelihood ratios, and diagnostic odds ratios, with 95% confidence intervals, were calculated. RESULTS Thirteen potentially relevant papers were retrieved (11 authors). Six authors agreed to share individual patient data. In total, 3681 patients were included. Three prediction tools (Osservatorio Epidemiologico sulla Sincope del Lazio [OESIL], San Francisco Syncope Rule [SFSR], Evaluation of Guidelines in Syncope Study [EGSYS]) could be assessed by the available datasets. None of the evaluated prediction tools performed better than clinical judgment in identifying serious outcomes during emergency department stay, and at 10 and 30 days after syncope. CONCLUSIONS Despite the use of an individual patient data approach to reduce heterogeneity among studies, a large variability was still present. Current prediction tools did not show better sensitivity, specificity, or prognostic yield compared with clinical judgment in predicting short-term serious outcome after syncope. Our systematic review strengthens the evidence that current prediction tools should not be strictly used in clinical practice.

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.

Priorities for emergency department syncope research

STUDY OBJECTIVES There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

First diagnosis of colorectal or breast cancer and prevalence of atrial fibrillation

Aim of the present study was to assess the prevalence of atrial fibrillation (AF) in patients with two different types of cancer. Recent epidemiologic and clinical studies support the hypothesis that AF is promoted and maintained by a broad spectrum of modulating factors. A total of 2,339 patients admitted to the Surgery Department of “Luigi Sacco Hospital, Milan,” over the period 1987–2004 were eligible for the study. One thousand three hundred and seventeen patients were admitted consecutively with a first diagnosis of colorectal or breast cancer (cases). The remaining 1,022 were patients admitted to undergo non-neoplastic surgery (controls). Routine pre-surgery electrocardiogram available in patient charts was analysed by a cardiologist who was not aware of the present study to evaluate the presence of atrial fibrillation or other arrhythmias. Overall, AF was present in 3.6% cases and 1.6% controls. This corresponded to at least two times higher likelihood of having AF in cases compared to controls. Prevalence of AF increased with age both in cases and controls. Our study describes an increased prevalence of AF in two different types of cancer. Autonomic, endocrine, coagulation, and inflammatory alterations were previously described in both AF and cancer, and can provide the physiopathological basis to our clinical observation.

Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases

HighlightsSleep deprivation (SD) can be due to lifestyle habits and sleep disorders.SD alters several mechanisms, i.e. autonomic nervous system, inflammation, endothelial dysfunction.SD are associated with increased risk of cardiovascular and metabolic diseases.An early diagnosis of sleep disorders is essential to prevent detrimental effects on health. ABSTRACT Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.

Systemic Inflammation, Atrial Fibrillation, and Cancer

To the Editor: The article by Chung et al1 reports a significant elevation of C-reactive protein (CRP) in patients with atrial fibrillation (AF). The CRP elevation was found both in patients with lone arrhythmia and in patients with structural heart disease. Moreover, the higher CRP levels were seen in patients with persistent, rather than paroxysmal, AF. We recently conducted a study to quantify the clinical observation of an unexpectedly high frequency of AF in patients with colorectal cancer.2 We considered a total of 1463 patients admitted to our Department of Surgery from 1987 to 1998 for surgical treatment of colorectal cancer (case …