A new echo-Doppler method to measure interatrial conduction time. Validation and clinical usefulness.

AIM: The aim of this study was to assess if knowing the interatrial conduction time is useful to better program atrioventricular delay in sequential pacing. The study proposes a new echo-Doppler method to measure interatrial conduction time, correlating it with electrophysiological measures. METHODS: The new method was tested in 30 subjects who underwent electrophysiological study. Interatrial conduction time by new method was taken during atrial pacing as the interval between the artefact of electrocardiogram pacing, shown on screen echo, and the onset of the A wave of the echo-Doppler mitral inflow. The electrophysiological measures were obtained, in the same subjects and at the same time, by a decapolar catheter in coronary sinus as intervals between the artefact of atrial pacing and the first positive left atrial deflection at proximal (C7C8) and distal (C1C2) electrodes. RESULTS: Echo-Doppler mean time was 114±12 ms, electrophysiological time was 107±14 ms at C7C8 and 124±11 ms at C1C2. Statistical analysis showed a good correlation (r=0.92, P<0.001) and accord (mean difference=6.6 ms) between the two methods. CONCLUSION: The new method to measure interatrial conduction time is consistent with the electrophysiological method; it could be particularly useful in programming the best AV delay in sequential and biventricular pacing, to avoid atrial contraction against a closed mitral valve.

Circulating endothelial progenitor cells in postmenopausal women with and without coronary artery disease.

BACKGROUND: Middle-aged women have a lower prevalence of coronary artery disease (CAD) compared with age-matched men, but mechanisms underlying this phenomenon remain controversial. To verify whether there is a link between circulating endothelial progenitor cells (EPCs) and gender-specific difference of CAD, we compared subpopulations of EPCs among postmenopausal normal women, patients with CAD, and age-matched men. METHODS: We studied 71 consecutive middle-aged patients with stable CAD (30 postmenopausal women and 41 men) and 40 middle-aged normal controls (20 postmenopausal women and 20 men). Blood samples were drawn at time of coronary angiography and subpopulations of EPCs were measured by flow cytometry. RESULTS: Women and men with CAD had similar age, risk factors, clinical presentation, left ventricular function, extension of CAD, and medical therapy at time of coronary angiography. Hematologic analysis showed that men and women with CAD had similar white cell count, mononuclear cells, and subpopulations of EPCs. Postmenopausal normal women, conversely, had significantly higher absolute numbers of CD34+, CD133+, CD105+ and CD14+ cells than other groups. CONCLUSIONS: Increased numbers of subpopulations of EPCs in normal postmenopausal women might contribute to the gender-specific difference of CAD in middle age. Lack of difference in EPCs between women and men with CAD suggests that stem cells become unable to play a protective role when the disease is clinically evident.

Randomised, double-blind, placebo-controlled, assessment of the efficacy and safety of dietary supplements in prehypertension.

We aimed to evaluate efficacy and tolerability of a protocol including lifestyle modifications and a novel combination of dietary supplements in prehypertension. A prospective, double-blind, randomised, placebo-controlled trial was conducted in 176 subjects (103 men, aged 52±10 years), with blood pressure (BP) of 130-139 mm Hg systolic and/or 85-89 mm Hg diastolic entered. After a single-blind run-in period, participants were randomised to twice daily placebo (n=88) or a commercially available combination pill (n=88). Primary endpoints were the differences in clinic BP between the two groups at the end of the trial. Secondary endpoints included intragroup differences in clinic BP during the study period and response rates (that is, BP <130/85 mm Hg or a BP reduction >5 mm Hg on week 12). Baseline characteristics were similar among the treatment groups. At 12 weeks, the supplement group had lower systolic BP (124±9 versus 132±7 mm Hg, P<0.0001) and similar diastolic BP (81±8 versus 82±7 mm Hg, P=0.382) compared to the placebo group. With respect to baseline measures, changes in BP with supplements were statistically significant for systolic (-9.3±4.2 mm Hg, P<0.0001) and diastolic values (-4.2±3.6 mm Hg, P<0.0001). Changes versus baseline in systolic and diastolic BP, conversely, were not different on placebo. The overall response rate at week 12 was significantly greater with supplements than placebo (58% (51 of 88) and 25% (22 of 88), respectively, P<0.0001). This randomised trial shows that combination of supplements with BP-lowering effect is an effective additional treatment to conventional lifestyle modifications for a better control of systolic BP in prehypertension.

Direct proinflammatory effect of C-reactive protein on human endothelial cells.

BACKGROUND: The acute-phase reactant C-reactive protein (CRP) is an important risk factor for coronary heart disease. However, the possible effects of CRP on vascular cells are not known. METHODS AND RESULTS: We tested the effects of CRP on expression of adhesion molecules in both human umbilical vein and coronary artery endothelial cells. Expression of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin was assessed by flow cytometry. Incubation with recombinant human CRP (10 microg/mL) for 24 hours induced an approximately 10-fold increase in expression of ICAM-1 and a significant expression of VCAM-1, whereas a 6-hour incubation induced significant E-selectin expression. Adhesion molecule induction was similar to that observed in endothelial cells activated with interleukin-1beta. In coronary artery endothelial cells, induction of ICAM-1 and VCAM-1 was already present at 5 microg/mL and reached a maximum at 50 microg/mL, at which point a substantial increase in expression of E-selectin was also evident. The CRP effect was dependent on presence of human serum in the culture medium, because no effect was seen in cells cultured with serum-free medium. In contrast, interleukin-1beta was able to induce adhesion molecule expression in the absence of human serum. CONCLUSIONS: CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of atherosclerosis.

Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed in atherosclerotic plaques and in endothelial cells. The possible effects of PPARgamma activators on endothelial activation and inflammatory response within the plaque are currently unknown. METHODS AND RESULTS: We tested the hypothesis that PPARgamma activators inhibit vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1) expression in cultured endothelial cells (evaluated by flow cytometry) and homing of monocyte/macrophages to atherosclerotic plaques in vivo. In endothelial cells, the PPARgamma agonists troglitazone at 100 micromol/L and 15-deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ2) at 20 micromol/L markedly attenuated the tumor necrosis factor-induced expression of VCAM-1 and ICAM-1. A significant inhibition of VCAM-1 expression was also evident at 5 and 10 micromol/L 15d-PGJ2 and 20 micromol/L troglitazone. Expression of E-selectin and PECAM-1 was not altered. To confirm the biological relevance of these results, we assessed the effects of troglitazone on monocyte/macrophage homing to atherosclerotic plaques in apoE-deficient mice. A 7-day treatment with troglitazone (400 mg/kg) significantly reduced monocyte/macrophage homing to atherosclerotic plaques (236+/-77 versus 177+/-43 macrophages, P=0.03); an even more striking inhibition was found at 3200 mg/kg troglitazone (344+/-76 versus 172+/-83 macrophages, P=0.005). CONCLUSIONS: PPARgamma activators inhibit expression of VCAM-1 and ICAM-1 in activated endothelial cells and significantly reduce monocyte/macrophage homing to atherosclerotic plaques. These findings suggest that PPARgamma activators, currently used in treatment of type II diabetes, may have beneficial effects in modulating inflammatory response in atherosclerosis.

Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs.

BACKGROUND: C-reactive protein (CRP) induces adhesion molecule expression by endothelial cells. However, the effects of CRP on chemokine expression by endothelial cells are not known. METHODS AND RESULTS: We tested the effects of CRP on the production of the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES in cultured human umbilical vein endothelial cells. The secretion of chemokines was assessed by ELISA. Incubation with 100 microgram/mL recombinant human CRP induced a 7-fold increase in MCP-1 but no change in RANTES secretion. We showed that the effect of CRP on MCP-1 was present even at 5 microgram/mL CRP, with stepwise increases as the CRP concentration was increased to 10, 50, and 100 microgram/mL. The effect of CRP on MCP-1 induction was not influenced by aspirin (at concentrations up to 1 mmol/L), but it was significantly inhibited by 5 micromol/L simvastatin. The peroxisome proliferator-activated receptor-alpha activators fenofibrate (100 micromol/L) and Wy-14649 (100 micromol/L) almost completely abolished the induction of MCP-1, but the peroxisome proliferator-activated receptor-gamma activator ciglitazone had only a moderate effect. CONCLUSIONS: These results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.

Role of different determinants of psychological distress in acute coronary syndromes.

OBJECTIVES: The aim of this study was to examine the prevalence of psychological distress and of its major determinants in acute coronary patients and in a control group. BACKGROUND: The prevalence and major determinants of psychological distress in acute coronary patients are not clear. METHODS: One hundred and thirty cardiac patients (110 men, age 56+/-9; 85 with acute myocardial infarction and 45 with unstable angina) and 102 controls hospitalized for acute trauma (70 men, age 55+/-9 years) were studied and the level of psychological distress estimated by a Modified Maastricht Questionnaire, self-ratings and ratings by a close relative. Major determinants of psychological distress were assessed by the Life Events Assessment, the Social Support Questionnaire and the Ways of Coping Checklist. RESULTS: The average level of psychological distress was significantly higher (p < 0.001) in coronary patients than in controls in all tests (self-evaluation=7.1+/-2.3 vs 4.3+/-2.4; relative-evaluation = 7.4+/-2.4 vs 4.2+/- 2.5; Modified Maastricht Questionnaire=91+/-32 vs 59+/-30). Cardiac patients reported significantly higher (p < 0.05) levels of social isolation (28.9+/-11.1 vs 23.4+/-8.8), self-blame (7.2+/-1.9 vs 5.8+/- 1.6) and avoidance (21.1+/-3.5 vs 18.9+/-3) and more painful life events (3.9+/-3.8 vs 2.6+/-2.2), than controls. However, not all patients had evidence of distress; indeed, cluster analysis identified a subgroup that comprised 75% of controls and 25% of cardiac patients with no determinants eliciting distress, while the other four subgroups, with one or more determinants of distress, comprised about 75% of patients and only 25% of controls. CONCLUSIONS: These results show that a high level of psychological distress is detectable in about 75% of patients with acute myocardial infarction or unstable angina and is related to one or more major determinants.

Autonomic changes associated with spontaneous coronary spasm in patients with variant angina.

OBJECTIVES: This study sought to investigate whether changes in nervous autonomic tone may have a role in the mechanisms triggering spontaneous coronary spasm in variant angina. BACKGROUND: Previous studies have suggested that both sympathetic and vagal activation may act as a trigger of epicardial artery spasm in patients with variant angina, but the actual role of autonomic changes in spontaneous coronary spasm remains unknown. METHODS: We analyzed the changes in heart rate variability associated with episodes of ST segment elevation detected on Holter monitoring in 23 patients with variant angina (18 men, 5 women; mean [+/-SD] age 59 +/- 12 years). For study purposes, episodes of transmural ischemia lasting > or = 3 min and without any ST segment changes in the previous 40 min were selected for analysis. Heart rate variability indexes were calculated at 2-min intervals, at 30,15,5 and 1 min before ST elevation and at peak ST segment elevation. Ninety-three of 239 total ischemic episodes (39%) fulfilled the inclusion criteria. RESULTS: The results showed that 1) high frequency (HF) (0.04 to 0.15 Hz), a heart rate variability index specific for vagal activity, decreased in the 2 min preceding ST segment elevation (p < 0.001) and returned to basal levels at peak ST segment elevation; 2) heart rate and low frequency (0.04 to 0.15 Hz), which are partially correlated with sympathetic activity, showed a significant increase at peak ST segment elevation (p < 0.001 for both); 3) the pattern of the HF reduction before ST segment elevation was consistently confirmed in several subgroups of ischemic episodes, including those of patients with or without coronary stenoses, those of patients with anterior or inferior ST segment elevation, those occurring during daily or nightly hours and silent episodes. There were no significant variations in heart rate variability in control periods selected from Holter tapes of patients and before ST segment elevation induced by balloon inflation in 20 patients undergoing coronary angioplasty. CONCLUSIONS: Our data show that changes in autonomic tone are likely to contribute to trigger or predispose to epicardial spasm. In particular, although not excluding an active role for adrenergic mechanisms, our data suggest that a vagal withdrawal may often be a component of the mechanisms leading to spontaneous coronary vasospasm.

Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X.

OBJECTIVES: We sought to investigate whether patients with syndrome X have an abnormal perception of cardiac pain. BACKGROUND: Previous studies have reported an increased sensitivity to potentially painful cardiac stimuli in patients with syndrome X. However, it is not clear whether this increase is due to an increased perception of pain or to an enhanced tendency to complain. METHODS: We assessed cardiac sensitivity to pain in 16 patients with syndrome X and 15 control subjects by performing right atrial and ventricular pacing with increasing stimulus intensity (1 to 10 mA) at a rate 5 to 10 beats higher than the patient's heart rate. False and true pacing were performed in random sequence, with both patients and investigators having no knowledge of the type of stimulation being administered. RESULTS: No control subject had pacing-induced pain; conversely, 8 patients with syndrome X reported angina during atrial pacing (50%, p < 0.01) and 15 during ventricular pacing (94%, p < 0.001). During atrial stimulation, both true and false pacing caused chest pain in a similar proportion of patients (50% vs. 63%, p = 0.61), whereas during ventricular stimulation, true pacing caused chest pain in a higher proportion of patients (94% vs. 50%, p < 0.05). Pain threshold and severity of pain (1 to 10 scale) were similar during true and false atrial pacing, whereas true ventricular pacing resulted in a lower pain threshold (mean +/- SD 3.7 +/- 3.0 vs. 7.9 +/- 2.8 mA, p < 0.001) and a higher level of pain severity (7.3 +/- 2.7 vs. 3.1 +/- 3.5, p < 0.001) than did false pacing. CONCLUSIONS: Patients with syndrome X frequently reported chest pain even in the absence of cardiac stimulation. Yet, in addition to this increased tendency to complain, they also exhibited a selective enhancement of ventricular painful sensitivity to electrical stimulation.

Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X.

The effects of a beta blocker (atenolol), a calcium antagonist (amlodipine), and a nitrate (isosorbide-5-mononitrate) on anginal symptoms in 10 patients with syndrome X were assessed in a crossover, double-blind, randomized trial. Only atenolol was found to significantly improve chest pain episodes, suggesting that it should be the preferred drug when starting pharmacologic treatment of patients with syndrome X.

Relation between myocardial infarction site and pain location in Q-wave acute myocardial infarction.

Location, severity, duration, and time course of pain were assessed in 104 consecutive patients with either first or second, anterior or inferior Q-wave acute myocardial infarction (AMI). Pain severity was assessed using a visual analog scale. Pain location and radiation were similar in 48 patients with anterior and 56 patients with inferior wall AMI. Pain duration (6.1 +/- 6.4 vs 6.5 +/- 5.4 hours, p = NS) and severity (68 +/- 21 vs 61 +/- 21 mm, p = NS) were also similar. The pain was continuous in 34 patients with anterior (71%) and in 42 with inferior (75%) wall AMI. Among the 41 patients who did not receive thrombolytic therapy, 18 patients with continuous pain had a higher creatine kinase peak level than the remaining 23 patients with intermittent pain or preinfarction angina, or both (2,065 +/- 1,017 vs 1,162 +/- 994 IU, p < 0.01). The incidence of gastrointestinal symptoms was slightly higher in patients with inferior than anterior wall AMI (70% vs 48%, p < 0.05). Among 32 patients admitted with a second AMI, pain location was similar in 14 who had both infarcts in the same myocardial region, but was different in 12 of 18 (67%) who had a first and second infarct in different regions (p < 0.001). Thus, patients with anterior or inferior wall AMI experienced pain in similar body regions. However, in patients who presented with > 1 AMI, different locations of the infarction pain were highly predictive of ischemia occurring in different myocardial regions. Finally, patients with preinfarction angina or intermittent pain tended to have smaller infarcts.

Ischemic-like ST-segment changes during Holter monitoring in patients with angina pectoris and normal coronary arteries but negative exercise testing.

To evaluate whether Holter electrocardiographic monitoring may improve the detection of ST-segment depression in patients with anginal chest pain and normal coronary arteries, we performed symptom-limited exercise testing and 24-hour Holter monitoring in a group of 38 such patients (27 women, age 54 +/- 8 years). Patients were divided into 2 groups:group X1 included 28 patients with and group X2 10 patients without significant ST-segment depression during exercise testing. There were no significant differences between the 2 groups in age, gender, characteristics of chest pain, exercise duration, heart rate (HR), and blood pressure at peak exercise, but anginal pain during exercise testing was reported by 10 patients of group X1 (36%) and 9 of group X2 (90%) (p <0.01). Episodes of ST-segment depression on Holter monitoring were found in 17 patients of group X1 (61%) and in 5 patients of group X2 (50%) (p = NS). There were no differences between the 2 groups in daily number of ST episodes (3.6 +/- 4 vs 2.8 +/- 5 episodes per patient), symptomatic episodes (8% vs 18%), and duration of the episodes. On average, HR increased significantly, in a similar way, from 15 minutes before ST-segment depression to 1-mm ST in both groups, and its value at the onset of ischemia was similar in the 2 groups (102 +/- 22 vs 109 +/- 18 beats/min, p = NS). Finally, HR at 1-mm ST during Holter monitoring was significantly lower than that observed at 1-mm ST during exercise testing (127 +/- 16 beats/min, p < or = 0.01) in group X1, and it was also lower than that observed at peak exercise (136 +/- 22 beats/min, p < or = 0.01) in group X2. In conclusion, Holter monitoring can significantly increase the detection of ST-segment depression in patients with anginal pain and normal coronary arteries, indicating a cardiac, although not necessarily ischemic, origin of the pain. Indeed, 50% of our patients with negative symptom-limited exercise testing showed spontaneous ST changes, compatible with transient myocardial ischemia, during daily activities. Differences in the response of coronary microvascular tone to exercise testing and to stimuli operating during daily life are likely to play a significant role in determining these findings.

Usefulness of the addition of heart rate variability to Holter monitoring in predicting in-hospital cardiac events in patients with unstable angina pectoris.

Transient ischemia on Holter monitoring is a major determinant of outcome in unstable angina. In this study we investigated whether analysis of heart rate variability (HRV) may further improve the prognostic yield of Holter monitoring in this clinical setting. We performed 24-hour Holter monitoring in 75 patients with unstable angina (59 men, aged 62 +/- 9 years) within 12 hours of hospital admission. Number and duration of myocardial ischemic episodes, and both time domain and frequency domain HRV measures were obtained from Holter recordings. In-hospital major cardiac events (death or myocardial infarction) occurred in 7 patients (9%). Episodes of ST-segment depression on Holter monitoring were found in 6 of 7 patients (86%) with and in 26 of 68 patients (38%) without events (p <0.05). There were no differences between patients with or without events in both time domain (standard deviation [SD] of all normal RR intervals in the entire 24-hour electrocardiographic recording (SDNN), SD of the mean RR intervals for all 5-minute segments (SDANN-i), mean of SD of all RR intervals for all 5-minute segments (SDNN-i), percentage of differences between adjacent RR intervals >50 ms (pNN50), and square root of the mean squared differences of successive RR intervals) (RMSSD), and frequency domain (ultra low, very low, low, and high frequency) HRV indexes. However, the low-frequency/high-frequency (LF/HF) ratio was significantly higher in patients with cardiac events (2.12 +/- 1.4 vs 1.48 +/- 0.5, p = 0.01). Moreover, when considering only the 32 patients with myocardial ischemic episodes on Holter monitoring, the LF/HF ratio was again higher in the 6 patients with than the 26 patients without major cardiac events (2.45 +/- 1.5 vs 1.31 +/- 0.3, p <0.01). Multivariate logistic regression, including clinical and angiographic variables, showed that transient ischemia on Holter monitoring was the only independent determinant of outcome (odds ratio = 12.2, p = 0.03), with the LF/HF ratio being only slightly over statistical significance (odds ratio for 0.1 increments = 2.8, p = 0.08). Our data confirm that transient ischemia on Holter monitoring is a powerful predictor of cardiac events in unstable angina and indicates that an imbalance in cardiac autonomic tone toward a prevalence of sympathetic activity increases the risk of events in this group of patients.

Cardiac autonomic function and sensitivity to pain in postmenopausal women with angina and normal coronary arteries.

An increased sensitivity to painful stimuli and an abnormal cardiac autonomic function have previously been reported in patients with angina and angiographically normal coronary arteries, a syndrome that mainly affects postmenopausal women. In this study we compared both general sensitivity to pain, by evaluating time to forearm ischemic pain (FIP) provoked by sphygmomanometer cuff inflation, and cardiac autonomic function, by measuring heart rate variability (HRV), and QT and QT(c) intervals on 24-hour Holter recordings, in 25 postmenopausal women with angina and normal coronary arteries and in 22 healthy postmenopausal women. Compared with controls, patients had a reproducible strikingly lower time to FIP (149 +/- 121 vs 295 +/- 158 seconds, p <0.001), whereas there were no differences between the 2 groups in HRV variables and mean 24-hour QT and QT(c) intervals. HRV indexes, and QT and QT(c) intervals also showed similar circadian patterns. Thus, our data show that postmenopausal women with angina and normal coronary arteries have an enhanced sensitivity to systemic painful stimuli, but no detectable impairment in cardiac autonomic function compared with a well-matched control group of postmenopausal healthy women.

Effects of atrial pacing on arterial and coronary sinus endothelin-1 levels in syndrome X.

Syndrome X may be caused by a coronary microvascular dysfunction, possibly due to abnormalities in coronary endothelial function. Previous studies suggested that endothelin-1 (ET-1) might be involved in the pathogenesis of syndrome X. Baseline arterial and coronary sinus ET-1 levels were measured in 13 patients with syndrome X (10 women, 52+/-7 years) and in 8 control patients (5 women, 46+/-11 years). ET-1 was also measured after atrial pacing in 12 patients with syndrome X and all controls. To simultaneously assess the activity of nitric oxide, guanosine 3'-5'-cyclic monophosphate (cGMP) was also measured in 11 patients with syndrome X and 7 controls. Baseline arterial (2.27+/-0.46 vs. 1.90+/-0.22 pg/ml, p<0.05) and coronary sinus (2.03+/-0.43 vs. 1.68+/-0.28 pg/ml, p = 0.06) ET-1 plasma levels were higher in patients than in controls. After pacing, arterial ET-1 levels did not change in either group and coronary sinus ET-1 levels were also unchanged in controls. In contrast, coronary sinus ET-increased significantly in response to atrial pacing in patients with syndrome X (p = 0.023), and differences between coronary sinus ET-1 levels of patients with syndrome X and controls after pacing became highly significant (2.22+/-0.45 vs. 1.69+/-0.20 pg/ml, respectively, p = 0.006). No significant differences in arterial and coronary sinus cGMP concentrations were found between the 2 groups, both at baseline and after pacing. Our findings suggest that an increased vasoconstrictor activity of microvascular endothelium is present in at least some patients with syndrome X and may be involved in the pathogenesis of the syndrome.

Prognostic role of heart rate variability in patients with a recent acute myocardial infarction.

A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction <40% and a number of ventricular premature beats > or = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio < 1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).

Helicobacter pylori is an aetiological factor for ischaemic heart disease: the case against.

Helicobacter pylori is one of four organisms often investigated for ari association with ischaemic heart disease. The four, including Chlamydia pneumoniae, Cytomegalovirus and Herpes virus, cause low-grade, life-long infections that can produce a persistent inflammation, the kind that leads to heart disease. Several studies suggest an association, but others suggest none. Patients with poor access to medical care are more likely to become infected and also more likely to suffer from coronary artery disease. Although the literature data are provocative and interesting, the two things may not be related. Helicobacter pylori infection is quite prevalent among individuals without ischaemic heart disease and absent in many of those with ischaemic heart disease. Thus, more definite answers about whether there is any link between Helicobacter pylori and cardiovascular disease are needed. It would be essential to establish the specific mechanisms that possibly confer vulnerability or protection toward coronaropathy. But a definite answer could come from clinical trials designed to test whether antibiotics can prevent the disease. Until now, no randomised trial has suggested a positive effect of Helicobacter pylori eradication in reducing the incidence of cardiac events.

Diagnostic accuracy of 320-row computed tomography as compared with invasive coronary angiography in unselected, consecutive patients with suspected coronary artery disease.

Noninvasive coronary angiography with multislice computed tomography (CT) scanners is feasible with high sensitivity and negative predictive value. The radiation exposure associated with this technique, however, is high and concerns in the widespread use of CT have arisen. We evaluated the diagnostic accuracy of coronary angiography using 320-row CT, which avoids exposure-intensive overscanning and overranging. We prospectively studied 118 unselected consecutive patients with suspected coronary artery disease (CAD) referred for invasive coronary angiography (ICA). All patients had 320-row CT within 1 week of ICA, which, together with quantitative analysis, served as the reference standard. Of the 65 out of 118 patients who were diagnosed as having CAD by ICA, 64 (98 %) were correctly identified at 320-row CT. Noteworthy, 320-row CT correctly detected CAD in 3 patients with atrial fibrillation and ruled out the disease in the other 8 patients. From 151 significant coronary stenoses detected on ICA, 137 (91 %) were correctly identified with 320-row CT. In the per-patient analysis, sensitivity and specificity of 320-row CT were 98 and 91 %, respectively. In the per-vessel analysis, sensitivity and specificity of 320-row CT were 93 and 95 %, respectively. In the per segment analysis, sensitivity and specificity of 320-row CT were 91 and 99 %, respectively. Diameter stenosis determined with the use of CT showed good correlation with ICA (P < 0.001, R = 0.81) without significant underestimation or overestimation (-3.1 ± 24.4 %; P = 0.08). Comparison of CT with ICA revealed a significantly smaller effective radiation dose (3.1 ± 2.3 vs. 6.5 ± 4.2 mSv; P < 0.05) and amount of contrast agent required (99 ± 51 vs. 65 ± 42 ml, P < 0.05) for 320 row CT. The present study in an unselected population including patients with atrial fibrillation demonstrates that 320-row CT may significantly reduce the radiation dose and amount of contrast agent required compared with ICA while maintaining a very high diagnostic accuracy.