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.

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.

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.

Comparison of verapamil and propranolol therapy for angina pectoris at rest: a randomized, multiple-crossover, controlled trial in the coronary care unit.

The effects of oral verapamil (V), 400 mg/day, oral propranolol (P), 300 mg/day, and placebo were compared in 10 patients admitted to the coronary care unit because of frequent attacks of angina at rest. Testing was done according to a randomized, double-blind, multiple-crossover, placebo-controlled trial, consisting of 8 consecutive 48-hour treatment periods with V or P or placebo. Three patients had variant angina, 5 had episodes of both ST-segment elevation and depression and 2 had only ST-segment depression. One patient had no critical coronary stenoses, 1 had 1-vessel disease, 7 had 2-vessel disease and 1 had 3-vessel disease. Electrocardiographic monitoring and tape recording were continued during the 16 days of the trial. A total of 1,602 episodes of transient diagnostic ST shift were recorded during the trial (1,309 episodes of ST-segment elevation, 293 of ST-segment depression); 43% were painless. Mean blood levels of V and P at the end of the active phases were 161 +/- 89 and 120 +/- 45 ng/ml, respectively. In the group as a whole, the average number of diagnostic ischemic ST-segment shifts per 24 hours was significantly reduced relative to corresponding placebo periods during V (2.6 +/- 2.4 vs 11.9 +/- 8.6; p less than 0.01) but not during P treatment (11.9 +/- 8.6 vs 12.0 +/- 7.3). Similar statistically significant reductions were observed in the number of anginal attacks and nitroglycerin tablets consumed. Considering individual patients, V reduced ischemic episodes during both active phases in all patients, whereas P was effective only in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Findings from long-term electrocardiographic monitoring of patients with variant angina in a coronary care unit.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

Regional and global biventricular function during dipyridamole stress testing.

This study assesses the relation between regional ventricular performance (using 2-dimensional echocardiography) and global systolic and diastolic indexes of biventricular myocardial function (using hemodynamic monitoring) during dipyridamole stress testing. Simultaneous 2-dimensional echocardiographic and biventricular hemodynamic monitoring during dipyridamole infusion (0.56 mg/kg over 4 minutes) was performed in 19 patients. All patients had a normal resting function. Eleven of the 19 patients had a positive echocardiography test (new wall motion dyssynergy with dipyridamole) and they formed group 1. Eight patients had a negative echocardiography test (group 2). During baseline conditions, no significant differences were found in the 2 groups: rate pressure product (107 +/- 16 vs 108 +/- 13 mm Hg x beats/min x 1/100), positive left ventricular (LV) dP/dt (1,950 +/- 473 vs 2,262 +/- 430 mm Hg/s), negative LV dP/dt (-2,069 +/- 620 vs -2,205 +/- 245), LV end-diastolic pressure (8.2 +/- 4.4 vs 9.6 +/- 4.0 mm Hg), right ventricular positive dP/dt (368 +/- 133 vs 400 +/- 190 mm Hg/s) and negative dP/dt (-281 +/- 89 vs -383 +/- 147). At peak dipyridamole, the 2 groups were different for LV end-diastolic pressure (20 +/- 10 vs 8 +/- 5 mm Hg, p less than 0.01), LV positive dP/dt (2,100 +/- 688 vs 3,013 +/- 851 mm Hg/s, p less than 0.01) and negative dP/dt (-1,868 +/- 518 vs -2,564 +/- 272, p less than 0.01). At peak ischemia, LV positive dP/dt increased slightly, but not significantly, while negative dP/dt decreased significantly (p less than 0.01) in comparison with resting values.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiparametric approach to diagnosis of non-Q-wave acute myocardial infarction.

The present study investigated whether the lack of enzyme increase is reason enough to exclude necrosis in patients with ischemic heart disease who develop electrocardiographic sustained ST-T changes in the absence of Q waves. In 15 consecutive patients with angina who developed sustained ST-T changes during hospitalization, the presence of myocardial necrosis was investigated by a prospective multiparametric approach. Serum enzymes and myoglobin, pyrophosphate uptake, 2-dimensional echocardiography, perfusion scintigraphy, left ventriculography and coronary angiography were evaluated. According to creatine kinase and creatine kinase-MB peak at twice the upper normal value, the diagnosis of acute myocardial infarction applied only to 40% of patients. However, myoglobin was positive in 80% and a perfusion defect could be documented by an electrocardiographic gated microsphere technique in 100% of patients. The positivity of myoglobin increased to 100% and of creatine kinase and creatine kinase-MB to 87 and 60%, respectively, when a peak value twice the individual lowest value was considered for positivity. The 100% presence of perfusion defects associated with the high prevalence of both positive pyrophosphate uptake (87%) and regional dyssynergies (87 and 73%, respectively, by left ventriculography and echocardiography) strongly suggest that sustained (greater than or equal to 7 days) ST-T changes in this population were indicative of myocardial necrosis. Thus, by conventional enzymatic approach, diagnosis of non-Q-wave infarction can be missed in a sizable number of patients and present important clinical implications.

Electrocardiographic monitoring: temporal versus spatial information and data processing.

In the diagnosis of ischemic heart disease, long-term electrocardiographic recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, furnishes the whole spectrum of electrocardiographic alterations accompanying ischemic attacks, reveals the possible ischemic genesis of dysrhythmias, and is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In addition to its valuable application in the screening and follow-up of ambulatory patients, its use in the Coronary Care Unit is of great interest, being in this context much more sensitive than visual electrocardiographic monitoring. In spite of these advantages, Holter monitoring has several limitations: the recording and replay systems are below recommended standards; the analysis of a single lead is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours, usually adopted for Holter monitoring, may not be sufficient for screening patients with suspected myocardial ischemia due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking and a reliable computerized analysis is needed to manage data overflow. In conclusion, although further research and technical developments are desired to improve reliability and data processing, the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

Myocardial cell damage during attacks of vasospastic angina in the absence of persistent electrocardiographic changes.

We have investigated whether vasospastic anginal attacks might be associated with myocardial cell damage even when permanent ORS or ST-T changes are absent. We obtained serum time-activity curves of creatine kinase MB, of myoglobin, and of alpha hydroxybutyrate dehydrogenase in 15 patients with vasospastic angina admitted to our Coronary Care Unit (CCU). A slight but consistent rise and fall of both myoglobin and creatine kinase MB was observed in 7 patients (4 presented a definitive myocardial uptake of 99mTc pyrophosphate, and I had a faint deposition). A similar pattern was observed for myoglobin alone in 3 patients (1 presented a negative myocardial scan), while no consistent changes were found in the remaining 5 patients (2 presented a faint deposition of 99mTc pyrophosphate). No significant change of alpha hydroxybutyrate dehydrogenase was observed in any of the patients. The coherent rise and fall of the levels of myocardial cytosolic components after prolonged episodes of vasospastic angina suggests that cell damage may occur even in the absence of persistent QRS and ST-T changes.

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.

Improvement of walking distance in patients with intermittent claudication by chronic local therapy with isosorbide dinitrate ointment.

Isosorbide dinitrate ointment (100 mg tid) was directly applied to 30 male patients with stable, documented intermittent claudication on the areas where ischemic pain was experienced. The symptom-free distance walked (DWA) and the maximum distance reached (MDR) basally, after one, three, six, and twelve months were evaluated by means of treadmill stress tests (TSTs) (angle 0 degree-velocity constant/patient). After the basal TST, patients were randomly divided into two groups: placebo group and therapy group (double blind), and a further TST was administered one month later. DWA results were 74 +/- 8 m vs 297 +/- 83 m and MDR results were 163 +/- 22 m vs 506 +/- 86 m in the therapy group (basal vs one month TST: p less than .01) and 94 +/- 24 m vs 96 +/- 15 m and 232 +/- 53 m vs 183 +/- 26 m in the placebo group, respectively (basal vs one month TST: NS). Being confident that a significant placebo effect was absent, the authors opened the trial and treated all patients, repeating further TSTs at three, six, and twelve months. The following results were obtained: DWA was 84 +/- 13 m, 316 +/- 63 m, 374 +/- 55 m, and 452 +/- 61 m; and MDR was 197 +/- 29 m, 431 +/- 59 m, 514 +/- 57 m, and 547 +/- 59 m, respectively, in basal conditions and after three, six, and twelve months of treatment (p less than .01 for all the values for both DWA and MDR vs basal values).(ABSTRACT TRUNCATED AT 250 WORDS)

Transient myocardial ischemia and cardiac pain. Importance of duration of ischemia, heart rate behaviour and circadian distribution.

In 40 drug-free patients 2052 episodes of transient myocardial ischemia (28% painful) were recorded by 24-h ambulatory ECG. Pain was more frequently associated with longer duration of ischemia and greater ST segment shift and with the presence of ventricular arrhythmias within the ischemic episode. Heart rate always showed a growing trend during the ischemic episode. Circadian distribution of painless ischemic episodes showed a maximum peak at 2 a.m. while the most painful attacks occurred early in the morning (6 a.m.).

Relationships between cardiac pain and objective markers of transient myocardial ischemia.

Cardiac pain is a key symptom for diagnosis of myocardial ischemia in man, even if a minority of transient myocardial ischemic episodes are painful. A multiparametric monitoring approach - associating non-invasive and invasive monitoring techniques during transient myocardial ischemia with and without pain - allows to achieve a clinical diagnosis and obtain information about the pathophysiology of the anginal syndrome.

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.

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.

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.

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.

Coronary flow and mental stress. Experimental findings.

The hemodynamic, electrocardiographic, and coronary flow responses to a psychological test were studied in 13 pigs both in the absence (group 1, n = 8) and the presence (group 2, n = 5) of a transient occlusion of the left anterior descending coronary artery. The psychological test consisted of presenting food to a fasting but restrained animal for 3 minutes. In group 1, stress increased the heart rate from 128 +/- 5 to 176 +/- 8 beats/min (mean +/- SEM) and arterial pressure from 93 +/- 4 to 112 mm Hg. Comparing the individual increase in rate-pressure product with the increase in coronary conductance during the test, a parallel response was found in only two animals, whereas a relatively lower coronary conductance was observed in the remainder, suggesting vasoconstriction. Clinical signs of ischemia or life-threatening arrhythmias were never observed in this group of animals. Each group 2 animal underwent two occlusions of the left anterior descending coronary artery, randomly performed on separate days both in the presence and the absence of the food deprivation stress. When the latter was applied in the presence of occlusion, all animals developed ventricular fibrillation in less than 2 minutes (mean, 81.4 seconds). Conversely, only one animal had ventricular fibrillation when a 3-minute occlusion was performed without exposure to stress. This occurred despite the fact that more severe ischemia (as detected by an increase in left ventricular end-diastolic pressure and decreases in dP/dt and systolic pressure) was recorded at 3 minutes of occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)