Prognostic role of heart rate in patients referred for coronary angiography: age and sex differences.

UNLABELLED: OBJECTIVE To evaluate the predictive value of resting heart rate (RHR) for cardiac and total mortality in a large population of patients referred for coronary angiography with an extended follow-up, stratified in four subpopulations according to gender and age (50th percentile corresponding to 67 years). METHODS: We studied 3559 subjects (2603 males, age: 66 ± 11 years, mean ± SD), obtaining patient data from the Institute electronic databank which saves demographic, clinical, instrumental and follow-up data of patients admitted to our department. RESULTS: During a mean follow-up period of 35 ± 25 months, 296 (8%) patients died; there were 173 (5%) cardiac deaths. In female patients irrespective of age, RHR (≥ 76 bpm, 75th percentile) did not appear predictive for cardiac death. In females, RHR was predictive for overall mortality after multivariate adjustment only in those aged ≥ 67 years (hazard ratio (HR) 1.7, 95% confidence interval (CI) 1-2.8, p ≤ 0.05). In male patients aged < 67 years, RHR remained as an independent predictive factor for overall mortality at the multivariate analysis (HR 2.5, 95% CI 1.5-4.2, p < 0.001), and as an independent predictor for both cardiac mortality (HR 1.8, 95% CI 1.2-2.7, p < 0.01) and total mortality (HR 1.6, 95% CI 1.2-2.3, p < 0.01) in male patients over 67 years. CONCLUSION: The current study suggests that the prognostic importance of RHR may differ according to the patient's gender and age, suggesting significant differences in cardiovascular physiopathology between female and male patients.

Radioprotection (un)awareness in cardiologists, and how to improve it.

In 2010 the International Atomic Energy Agency launched the "3 A's campaign": Audit, Appropriateness and Awareness for radiological justification, which is an effective tool for cancer prevention. Cardiologists prescribe the majority of radiological testing, but their awareness of doses and risks of ionizing cardiac imaging test is low. To assess radioprotection awareness of prescribing and practicing physicians (mainly cardiologists) before and after a radioprotection course. We held a 1-day 6-h primer of radioprotection for a limited number (20-35) of physicians. The course offered 8 continuing education credits from the Italian Health Ministry and was held 9 times over 3 years. We had 425 attendees, but full data sets (with complete questionnaires) were available for 403 physicians (55% women, age 45 ± 6 years), including 55% cardiologists, 40% general practitioners, 5% others (mainly cardiology fellows). For each attendee, a radiological awareness score was obtained before and after the course, with a survey containing 10 multiple-choice questions (5 answers) on radioprotection basics (doses of common examinations in multiples of chest x-rays; associated cancer risk, etc.). Each answer was scored from 0 ("don't know"), 1 ("strongly disagree") to 4 ("strongly agree"). The radiological awareness score of the 403 attendees improved from 31 ± 3 (before) to 37 ± 2 (after training, P < 0.001 vs. pre-training). As an example, before training, 25% of attendees believed that radiation-induced cancer risk disappears after 6 months (10% of respondents), 12 months (8%) or 5 years (7%), whereas 75% (becoming 98% after training) correctly estimated that radiological damage is cumulative over one's lifetime. Awareness of radiological doses and risks, albeit essential for risk-benefit assessment of radiological testing, is suboptimal among cardiologists, but can dramatically improve with a limited teaching effort through targeted training.

Thyroid hormone, amiodarone therapy, and prognosis in left ventricular systolic dysfunction.

BACKGROUND: Amiodarone protects patients with left ventricular systolic dysfunction (LVSD) against serious arrhythmias, but it also has numerous side effects on non-cardiac organs, such as the thyroid. Indeed, amiodarone may inhibit the peripheral conversion of T4 into T3. Pathologically reduced serum levels of T3 - the so-called "low T3 syndrome" (LOWT3) - increase mortality in patients with LVSD and not on amiodarone. AIM: The aim of the study was to examine the relationship between thyroid hormone status, amiodarone therapy, and outcome in a population with LVSD. MATERIAL/ SUBJECTS AND METHODS: A total of 2344 patients with LVSD and free of overt hyper- and hypothyroidism were enrolled. The population was divided into 4 groups: group 1 (LOWT3 and amiodarone therapy, no.=126), group 2 (isolated amiodarone therapy, no.=74), group 3 (isolated LOWT3, no.=682), group 4 (controls, no.=1462). RESULTS: Kaplan-Meier curves showed, after a mean follow-up of 31 months, increased total and cardiac mortality in groups 1 (30% and 20%, respectively), 2 (23%, 11%), and 3 (22%, 12%) compared to group 4 (total mortality log-rank 82.8, p<0.0001; cardiac mortality log-rank 63.1, p<0.0001). At Cox analysis, adjusted for several clinical variables, survival was reduced in groups 1 and 3 compared to group 4. Group 2 had a similar mortality to group 4, although the number of patients was too limited to accurately assess the effect of amiodarone on long-term prognosis. CONCLUSIONS: LOWT3 exerts an adverse impact on prognosis in LVSD, which is not influenced by concomitant amiodarone therapy.

Impaired sympathetic response before intradialytic hypotension: a study based on spectral analysis of heart rate and pressure variability.

The purpose of this study was to evaluate the autonomic response to standard haemodialysis and the changes associated with the onset of intradialytic hypotension in 12 normotensive patients with uraemia. Power spectra of R-R interval and of blood pressure fluctuations were obtained during a standard dialysis session and estimated in the low-frequency (LF, 30-150 mHz) and high-frequency (HF, 150-400 mHz) range. The absolute power of the LF component of blood pressure variations and the LF/HF ratio of R-R interval were assumed as indexes of sympathetic activity. Standard haemodialysis induced hypotension in six patients (unstable) while a minor pressure decline was present in the other six (stable). Normalized blood volume before dialysis and percentage volume reduction were similar in the two groups. Tachycardia in response to pressure and volume decrease was more pronounced in stable than in unstable patients, as evidenced by a higher slope of the relation between R-R interval and systolic blood pressure (7.9 versus 0.9 ms/mmHg, P<0.01). Sympathetic tone was enhanced during early dialysis in all patients (+2+/-1 for R-R LF/HF ratio, +2.4+/-0.6 mmHg2 and +7.2+/-2 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05), compared with baseline predialysis values. During late dialysis, unstable patients showed an impairment of sympathetic activation which preceded hypotension and was maximal during the crisis (-2.9+/-1.4 for R-R LF/HF ratio, -2.7+/-1.4 mmHg2 and -8.6+/-4.0 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05). On the contrary, stable patients showed constantly elevated indexes (+3.7+/-1.4 for R-R LF/HF ratio, +5.9+/-2.7 mmHg2 and +13.3+/-6.2 mmHg2 for LF of diastolic and of systolic blood pressure, P<0.05). Values returned to predialysis levels after the end of the dialysis session in all patients. We conclude that standard haemodialysis activates a marked and reversible sympathetic response in both stable and unstable uraemic patients. However, in unstable patients, such activation is impaired in late dialysis, therefore contributing to the onset of the hypotensive crisis.

Safety of ergotamine-ergic pharmacologic stress echocardiography for vasospasm testing in the echo lab: 14 year experience on 478 tests in 464 patients.

BACKGROUND: The safety of ergonovine/ergometrine stress testing for coronary vasospasm when performed outside the cath lab has vigorously been questioned. The aim of this study was to assess the value of ergonovine/ergometrine stress testing performed in the echo lab. METHODS: We retrospectively reviewed the data prospectively collected in the echo lab of the Institute of Clinical Physiology of Pisa (Italy) from January 1, 1985, to October 1, 1998, on 478 tests performed on 464 patients with either ergonovine or ergometrine stress echo testing. By selection, all patients had history of chest pain, consistent with vasospastic angina, negative or ambiguous exercise stress testing, and normal or near normal resting left ventricular function. Ergonovine or ergometrine maleate was injected up to a total cumulative dosage of 0.35 mg, under continuous 12 lead ECG and two-dimensional echo monitoring. RESULTS: There were no death, myocardial infarction, ventricular fibrillation or III degree atrioventricular block. One patient had non-sustained ventricular tachycardia associated with transient ST segment elevation 30 min after the test. Two patients had II degree atrioventricular block, associated with positive echocardiography test and promptly reversed by nitrate administration. Transient regional myocardial dysfunction occurred in 74 patients (15%). Limiting ischemia-independent side effects were present in 13 patients (3%): hypotension in 1, arterial hypertension in 5, nonsustained ventricular tachycardia in 2, and nausea/vomiting in 5. The overall feasibility was 97%. CONCLUSIONS: Pharmacological stress echocardiography with either ergonovine or ergometrine is highly feasible and can be safely performed in the echo lab in properly selected patients in whom coronary vasospasm is suspected. It is often the only way to document coronary vasospasm otherwise missed by conventional noninvasive stress test and even by coronary angiography.

C3: Java-based medical record system for cardiology.

This paper describes a system for electronic medical record (EMR) we have developed for use in our health care institution, mainly dealing with diagnosis and treatment of cardiovascular pathologies. This activity is part of the project SPERIGEST, supported by Health Ministry of Italy, for the management of health care delivery, as concerns both clinical and administrative aspects. A networked computer-based information system was realized to integrate the different heterogeneous sources of patient information. Both clinical and administrative patient relevant data are provided from the various systems and stored into a central database. The EMR system was designed using World Wide Web (WWW) technology (Java, HTML). The system is currently under clinical evaluation.

Autonomic and hemodynamic responses to insulin in lean and obese humans.

To study the acute effects of insulin on autonomic control of cardiac function, we performed spectral analysis of heart rate variability and measured cardiac dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg.m-2) and 14 lean (BMI = 24 +/- 1 kg.m-2) subjects in the basal state and in response to physiological hyperinsulinemia (1 mU.min-1.kg-1 insulin clamp). In the lean group, insulin promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes were twice as large as accounted for by the concomitant changes in heart rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, stroke volume (67 +/- 4 to 76 +/- 9 ml.min-1) and cardiac output (4.45 +/- 0.21 to 5.06 +/- 0.55 l.min-1) rose, whereas peripheral vascular resistance fell. The low-to-high frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P < 0.01), indicating sympathetic shift of autonomic balance. In the obese group, all basal spectral powers were significantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency ratio was higher than in controls at baseline (2.4 +/- 0.4, P < 0.03), and failed to increase after insulin (2.2 +/- 0.3, P = ns). Furthermore, obesity was associated with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min-1, P < 0.01) and cardiac output (6.01 +/- 0.31 vs. 4.45 +/- 0.21 l.min-1, P = 0.001) but lower peripheral vascular resistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P = 0.002), whereas mean arterial blood pressure was similar to control (90 +/- 2 vs. 86 +/- 2 mmHg, P = not significant). We conclude that physiological hyperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and para-sympathetic stimuli, sympathetic shift of autonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, and may therefore be linked with chronic hyperinsulinemia.

Autonomic dysfunction in systemic sclerosis: time and frequency domain 24 hour heart rate variability analysis.

To evaluate the autonomic nervous control of the heart in patients with systemic sclerosis (SSc), spontaneous heart rate variability was investigated by means of time-domain and spectrum analysis of 24 h ECG ambulatory recordings in 30 SSc patients (four males, aged 45.2 +/- 9 yr, mean +/- S.D., range 27-60) and 30 age-matched healthy subjects. A significantly higher heart rate (P < 0.01) and lower circadian and spectral indices of heart rate variability (P < 0.01) were observed in SSc patients, compared with controls. A predictive value of age (P = 0.002), tachycardia (P = 0.002), circadian heart rate variability (P = 0.0025) and spectral power values (P = 0.005) for patient mortality was found. Moreover, the relative risk of death was higher (P = 0.05) in older subjects with circulating anti-Scl70. These abnormalities, detectable by a feasible, non-invasive diagnostic approach, indicate the presence of autonomic cardiac neuropathy in SSc patients.

Detection of nonlinearity in the healthy heart rhythm.

Sequences of interbeat intervals from two groups of subjects, 24 in relaxed and 10 in sleeping condition were analyzed by the nonlinear predictor method as well as by a method, proposed recently, able to directly estimate the time series nonlinearity. The nonlinear predictability of the R-R intervals is tested by using surrogate data. The results obtained with both methods show that nearly all the sequences exhibit a statistically meaningful degree of nonlinearity. This raises the question whether such nonlinearity encodes information about the physiological condition of the examined subjects.

Cattell's 16 PF and PSY inventory: relationship between personality traits and behavioral responses in patients with acute myocardial infarction.

The aim of this study was to investigate the relationships between personality and behavioral responses in patients with acute myocardial infarction. In a first step, a new instrument (PSY Inventory) for assessment of six behavioral characteristics (Sense of Responsibility, Energy and Competitiveness, Obsessive Behavior, Anger and Hostility, Stress-related Disturbances, Time Urgency) was developed by using factor analysis on intercorrelations of responses from 524 subjects of the general population. Internal consistency reliability for each of the PSY subscales was estimated by Cronbach alpha coefficients. In a second step, the PSY Inventory was administered with the Cattell 16 PF Questionnaire to 838 patients affected by acute myocardial infarction. Significant correlations although relatively low in magnitude for PSY Inventory subscales and certain scales of the Cattell 16 PF were found. With factor analysis on 22 variables (including the six PSY Inventory subscales and the 16 scales of the Cattell 16 PF), five second-order factors were identified, namely, Extraversion, Neurotic Anxiety, Superego Strength, Pathemia, and Neurotic Hostility. While a Pathemia Factor (characterized by sensitivity, imagination, and self-sufficiency) was factorially independent of scales of the PSY Inventory, Extraversion, Neurotic Anxiety, Superego Strength, and Neurotic Hostility Factors were composed of the PSY Inventory scales and Cattell 16 PF scales combined. These relationships would reflect the concordance of internal constructs for behavioral measures of the PSY Inventory and those of personality traits of the 16 PF Questionnaire in patients with acute myocardial infarction.

Ergonovine-echo test to assess the significance of chest pain at rest without ECG changes.

The aim of this study was to assess the feasibility and diagnostic role of ergonovine maleate infusion under continuous two-dimensional echocardiographic monitoring for the identification of vasospastic myocardial ischaemia in patients with chest pain at rest not associated with diagnostic ECG changes. One hundred and twenty-eight consecutive patients, selected on the basis of absence of ischaemic ECG changes during angina at rest before or during hospitalization, were enrolled in the study. Ergonovine maleate was i.v. administered in scaled doses (from 0.025 to 0.2 mg at 10 min intervals) under echocardiographic, electrocardiographic and systemic blood pressure monitoring. Wall motion asynergies were observed in 33 patients, accompanied by typical chest pain in 24 patients and by ECG changes in 25 (ST elevation in 13 patients, ST depression in seven, T wave changes in five). All patients were able to complete the test. Non life-threatening ventricular arrhythmias were observed in four patients exclusively in association with ischaemia. In seven patients with a positive test, coronary artery spasm was documented at angiography. In 16 patients with a positive test, the vasospastic event was reproduced by a hyperventilation-echo test or a second ergonovine maleate-echo test performed within 3 days of the first examination. In none of the patients with a negative test was documentation of myocardial ischaemia due to a primary reduction in coronary blood flow. Thus, in patients who do not show ECG changes during chest pain at rest, the ergonovine maleate-echo test is feasible and safe; it permits the recognition of ischaemic episodes on the basis of wall motion abnormalities when conventional 12-lead ECG-recorded chest pain is non-diagnostic.

The second-order factor structure of Cattell's 16 PF in patients with coronary heart disease.

The second-order factor structure of the 16 Personality Factor Questionnaire (16 PF) was validated on a sample of 940 patients hospitalized for coronary heart disease. The purpose of this investigation was the evaluation of second-order factor structure, already confirmed for normal subjects, of a selected pathological population. With factor analyses, oblique promax rotation, five second-order factors were identified, namely, Anxiety, Extraversion, Pathemia, Control, and an unidentified factor. These results were compared with those of Cattell's and Krug's studies. As a high congruence coefficient was shown, a good replication of Cattell's originally published second-order factors was achieved.

[Personality and acute myocardial infarction: distinctive traits]. / Personalitè ed infarto miocardico acuto: tratti discriminanti.

AIM OF THE STUDY: Aim of this study is to evaluate the presence of peculiar personality traits in patients with acute myocardial infarction as compared with normal subjects. METHODS: The Sixteen Personality Factor Questionnaire (16 PF) by Cattell (D form) is administered to 654 patients (558 males, 96 females) hospitalized for acute myocardial infarction in 16 coronary care units and to 398 normal subjects (261 males, 137 females). The diagnosis of myocardial infarction is made according to the presence of at least two of the following criteria: prolonged chest pain, elevation of CPK and CPKMB (twice the upper normal values), Q wave on the electrocardiogram. The normality of the control group is assured by specific exclusion criteria (cardiac or psychiatric disease, metabolic and endocrine disease, continued therapeutic treatment for any organic disease, or continued assumption of hypnotic and/or anxiolytic drugs). RESULTS: In comparison with the control group, infarcted males result significantly different for factors C, N, Q1, Q4 (p < 0.001), for factors B, O (p < 0.01) and A, H, I (p < 0.05). Females with myocardial infarction differ significantly for factors C, O and I (p < 0.05). Four second-order factors is obtained from Cattell's 16 PF by factorial analysis: QI (anxiety), QII (extroversion), QIII (sensitivity), QIV (superego strength). The infarcted population shows statistically significant differences compared with controls: infarcted males show higher QI (p < 0.001) and lower QII and QIII (p < 0.05) while infarcted females have higher QI (p < 0.05). CONCLUSIONS: These differences confirm that peculiar personality traits can be found in patients with acute myocardial infarction. In particular, infarcted males are emotionally unstable, anxious, rigid and depressed, and have problems in communication with others; infarcted females differ from the normal population for being emotionally unstable, anxious and for having a less flexible mental disposition. The higher anxiety level in patients with acute myocardial infarction may be related to the neuroticism that, in other studies, has been often found to be associated with cardiovascular disease. In conclusion, with respect to the normal population, patients with acute myocardial infarction appear to be anxious introverts, with conflictual personality.

Immunoradiometric assay of serum myosin as a marker of myocardial cell damage: methodological and clinical evaluation.

We evaluated the performance and analytical parameters of a one-step magnetic IRMA kit for the measurement of myosin in serum. The method uses two monoclonal antibodies selected for their high affinity to the heavy chains of human ventricular myosin. The first antibody is coupled to a magnetic solid phase and the second one is labeled with 125I. The working range of the IRMA (range of myosin concentrations measured with an imprecision < 10% CV) was 250-3600 microU/L and the sensitivity 20.8 +/- 7.2 microU/L. The between-assay variability, evaluated from replicate measurements in different runs of two serum pools was 14.6 CV% for the first pool (259.1 +/- 37.8 microU/L) and 14.3 CV% for the second pool (442.0 +/- 63.1 microU/L), respectively. To evaluate the clinical usefulness of myosin as a marker of myocardial cell damage, serum myosin was measured in patients with acute myocardial infarction (AMI) (n = 9) or subarachnoid hemorrhage (n = 20). The results obtained with the myosin assay were compared with those of two other markers considered specific for myocardial necrosis (CK-MB and myoglobin). In eight patients with AMI, serum myosin was elevated 24-36 hours after the onset of chest pain and reached a maximum at 4-7 days, returning to control levels at 8-11 days. The one remaining AMI patient showed two subsequent peaks in serum CK-MB and myoglobin concentrations (thus suggesting an extension of myocardial necrosis), the myosin concentrations reaching their peak only after 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Cryoblockade in limbic brain (amygdala) prevents or delays ventricular fibrillation after coronary artery occlusion in psychologically stressed pigs.

Neomammalian and paleomammalian (limbic) brain structures control different behaviors and the autonomic support specific to each. Both neural systems are involved in cardiovascular disorders. Our previous studies showed that bilateral cryoblockade of a neomammalian structure (the frontal lobes) reduces blood pressure elevations in experimental hypertension and prevents lethal arrhythmogenesis in experimental myocardial infarction. Other studies showed that bilateral lesions in a paleomammalian structure (amygdala) also reduce the blood pressure elevations. Thus, we hypothesized that cryoblockade of the amygdala would prevent lethal arrhythmogenesis. We found that cooling of cryoprobes implanted bilaterally in the amygdala prevented ventricular fibrillation in five of eight pigs during a 20-minute period of reversible myocardial ischemia, whereas cryoblockade in structures surrounding the amygdala (five pigs), unilateral cryoblockade in the amygdala (two pigs), or sham operations (three pigs) did not prevent ventricular fibrillation (p less than 0.003). In two of the five pigs with amygdaloid blockade, the cooling was reversed at 20 minutes while the coronary occlusion continued (24 hours), and still ventricular fibrillation did not occur. In all other cases, ischemia was reversed at 20 minutes so that the heart could recover; this enabled histochemical documentation that the heart was normal at the time(s) ischemia was induced, and it allowed within-subject control experiments. Amygdaloid cryoblockade produced a small but significant increase in heart rate (10 beats per minute) without a change in blood pressure. We conclude that the paleomammalian brain, like its neomammalian counterpart, mediates brain effects on fatal arrhythmogenesis.

Correlation dimension of heartbeat intervals is reduced in conscious pigs by myocardial ischemia.

A reduced standard deviation of RR intervals (SDRR) predicts increased mortality in groups of survivors of myocardial infarction. Like SDRR, the correlation dimension (D2) describes variation within a sampled time series, but uniquely it reveals 1) the epoch's geometric structure and 2) the degrees of freedom of the generator. These unique features may be more sensitive predictors of mortality than SDRR. We developed a new algorithm for estimating D2 (i.e., the "point-D2"), tested it with known data, and found that it had greater accuracy for finite data than other published algorithms. Analysis of RR intervals from eight conscious pigs undergoing acute occlusion of the left anterior descending coronary artery revealed a drop in the point-D2 from a control mean and standard deviation of 2.50 +/- 0.81 to 1.58 +/- 0.64 during the first minute of ischemia (p less than 0.01) and to 1.07 +/- 0.18 during the last minute preceding ventricular fibrillation (p less than 0.01). Partial occlusions (50-90% reduction of coronary blood flow) evoked point-D2 reductions only 25-30% of control (p less than 0.01). The point-D2 means were correlated between pigs with the magnitude of the respiratory sinus arrhythmia (p less than 0.01), but during ischemia this correlation was replaced by one between the standard deviation of the point-D2s and SDRRs. Because the simultaneous reduction in the mean point-D2 and its standard deviation to 1.07 +/- 0.18 occurred in every case, was unique to the few minutes preceding ventricular fibrillation, and never reached these low values during other conditions in which it was reduced, we conclude that the point-D2 may be an accurate prospective predictor of mortality within the individual subject.