Effect of angiotensin-converting enzyme inhibitor on collagenolytic enzyme activity in patients with acute myocardial infarction.

Matrix metalloproteinases and their tissue inhibitors are key enzymes degrading myocardial collagen in acute myocardial infarction (AMI). The aim of the present study was to determine whether angiotensin-converting enzyme inhibitors (ACEI) influence collagenase-1 (MMP-1) and their tissue inhibitor (TIMP-1) activity in AMI patients. Plasma levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured in 24 patients (aged 58.4 +/- 13.9 years) with AMI. Thirteen patients received perindopril 4 mg/day (group A) and 11 did not (group B). Plasma samples collected on admission and at 0, 3, 6, 9, 12, 18, 24, 36 and 48 hours and on days 3, 4, 5, 7, 15 and 30 thereafter were analyzed by relevant ELISA kits. Ejection fraction (EF) was assessed by ventriculography and end-diastolic diameter (EDD) echo-study on days 6 and 30. Values of collagenolytic enzymes of group A compared with those in group B were on average lower by 34%, 18.3% and 40%, respectively. The difference in values between groups at 0 h, 3 h and 9 h was significant (p < 0.048). ANOVA repeated measurement analysis showed significance within subjects for MMP-1 alone (p < 0.043) and for MMP-1 and ACEI (p < 0.046), while for TIMP-1 and MMP-1/TIMP-1 complex significance was only p < 0.0009. Regarding EDD changes, patients in group A showed minimal or no changes (51.23 +/- 1.8 mm to 51.6 +/- 2.13 mm), their EF was 38.8% and infarct size was medium to large. In contrast, group B showed a trend to increase EDD (41 +/- 0.78 mm to 42.33 +/- 0.59 mm), their EF was 50.5% and infarct size was small to medium. In conclusion, early initiation of ACEI treatment reduces collagenolytic activity. This effect may be considered an alternative mechanism for beneficial effects on postinfarction remodeling.

The association between occupational stress and the risk of developing acute coronary syndromes: the CARDIO2000 Study.

OBJECTIVE: The aim of this study was to investigate the association between occupational stress and the risk of developing acute coronary syndromes, in a population-based sample of patients and controls. METHODOLOGY: During 2000-01, a case-control study was conducted (CARDIO2000). A random and stratified sample of 848 middle aged patients with a first of an acute coronary syndrome and 1078 cardiovascular disease free participants, matched with the patients by gender, age and region, was selected from all regions of Greece. In addition to the common cardiovascular risk factors, the effect of occupational stress on coronary risk was evaluated, after taking into account income, marital status, educational and occupational level of the participants. The levels of occupational stress were measured by administering to the individuals a self-reported questionnaire. RESULTS: After controlling for age, gender and region, by design, and the presence of smoking, hypertension, hypercholesterolaemia, diabetes mellitus, physical activity status, educational and financial status and nutritional habits, multivariate analysis showed that the levels of occupational stress are positively associated with the risk of developing acute coronary syndromes in the investigated sample (Odds Ratio = 2.2, p < 0.01). Moreover, the presence of occupational stress seems to affect more significantly males than females, smokers than non-smokers, hypertensives than normotensives and high alcohol consumers compared to low alcohol consumers. CONCLUSIONS: Although the design of the present study does not provide evidence of causality, a strong positive association between occupational stress and acute coronary syndromes seems to exist. Thus, public health policies should take into account lifestyle conditions related to work in the design of preventive strategies at the primary level.

Neurocardiogenic syncope: aetiology and management.

Neurocardiogenic syncope is the most common cause of syncope presenting in the outpatient setting. It is usually encountered among individuals without an underlying heart disease, but not uncommonly participates in the syncope mechanism of patients with an obstructive or an arrhythmic cardiac cause for syncope as well. The vasovagal event is caused by a transient profound hypotensive reaction most commonly associated with inappropriate bradycardia resulting from activation of a complex autonomic reflex. The pathophysiology of neurocardiogenic syncope has been elucidated by tilt table testing, a noninvasive and well-tolerated method for reproducing the event in susceptible individuals. Although the majority of people with vasovagal fainting need no specific treatment, treatment is required for those presenting with problematic features such as frequent events accompanied by trauma or accidents, and occasionally by a severe cardioinhibitory pattern response. A number of different drugs have been proposed to favourably act on different aspects of the neurocardiogenic reflex but only a few randomised, placebo-controlled, drug-specific trials are currently available. Alternatively, cardiac pacing has also been introduced for patients who have symptoms that are drug-refractory or for those with a severe cardioinhibitory hypotensive response. The selection of the appropriate treatment plan should be individualised after consideration of patient history, clinical characteristics and preference, results of the baseline tilting study, and the existing evidence from the few randomised, controlled studies performed so far.

In-hospital mortality of habitual cigarette smokers after acute myocardial infarction; the "smoker's paradox" in a countrywide study.

AIMS: Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with acute myocardial infarction. METHODS AND RESULTS: The study population was derived from the registry of the Hellenic study of acute myocardial infarction, which recruited 7433 consecutive patients with acute myocardial infarction from 76, out of a total of 86, hospitals countrywide. Cigarette smokers presented with lower unadjusted mortality rates (7.4% vs 14.5%, P<0.001), were younger, predominantly of male gender and were less likely to suffer from diabetes mellitus and arterial hypertension. When all univariate predictors of poor outcome were included as covariates in multivariate analysis, smoking status was not significantly associated with inhospital mortality (relative risk=1.12, 95% CI=0.86-1.44, P=0.399). The beneficial effect of thrombolytic therapy was independent of the smoking status in both univariate and multivariate analysis. CONCLUSION: Unadjusted mortality rates are significantly lower in smokers, but age accounted for much of their seemingly improved outcome. When a number of additional clinical variables were taken into consideration, no significant influence of habitual smoking on early outcome following acute myocardial infarction was observed.

Increased temperature of malignant urinary bladder tumors in vivo: the application of a new method based on a catheter technique.

PURPOSE: The aim of this study was to investigate the existence of any thermal difference between malignant tumors and inflammatory benign lesions of the human urinary bladder and to determine whether it correlates with tumor angiogenesis quantification. PATIENTS AND METHODS: A new method, developed in our institute, is introduced to detect temperature in human urinary bladder, in vivo. This method is based on a thermography catheter. We calculated the differences of the temperature of the solid tumor and of a normal area (Delta T) on 20 subjects (mean age, 72.5 years; 95% confidence interval [CI], 68.5 to 76.4). According to the biopsy histology, Eight (40%) patients had benign tumors, and 12 (60%) had malignant tumors. RESULTS: We found significant differences of Delta T between patients with benign and malignant tumor (P <.001). Also, differences were found for the mean values of angiogenesis level between malignant and benign tumors (P =.0261), and a moderated positive correlation was estimated between the degree of angiogenesis and Delta T (P =.02). Based on logistic regression analysis, we found that a 1-degree increase of Delta T triples the odds of a patient having a malignant tumor (odds ratio = 2.91; 95% CI, 1.97 to 7.78; P <.001), adjusted for the degree of angiogenesis (P =.0236) and the grade of tumor (P <.001). A threshold point of Delta T = 0.7 degrees C was determined, with sensitivity 83% and specificity 75%. CONCLUSION: These findings suggest that the calculated difference of temperature between normal tissue and neoplastic area could be a useful criterion in the diagnosis of malignancy in tumors of the human urinary bladder.

Evolutionary pattern and prognostic importance of heart rate variability during the early phase of acute myocardial infarction.

AIMS: To investigate the evolution of time domain heart rate variability in the early phase of acute myocardial infarction (MI) and assess its prognostic ability. METHODS: We analysed several measures of heart rate variability (SDNN, SDANN, SDNN index, RMSSD) in 138 patients at days 0, 1 and 5+/-1 after hospital admission for acute MI. Results were correlated with infarct site, clinical variation and clinical outcome (death, MI, PTCA, CABG surgery). RESULTS: Measures of heart rate variability (SDNN, SDANN and SDNN index) declined during the first 24 h after acute MI (P<0.01) and increased to admission levels after about 5 days. SDNN values on day 0, 1 and 5 respectively were: 86+/-35, 75+/-28 and 87+/-27 ms. Patients with anterior infarction had lower heart rate variability than patients with inferior infarction on all test days but similar evolution patterns. After 3 years of follow-up there were 12 cardiac deaths (8.7%) and six resuscitated arrests and 33 (24%) new MIs, or revascularisation procedures. The evolutionary pattern of heart rate variability was similar in survivors to those who died although values were generally lower. Mortality was significantly higher in the group with SDNN<50 ms at day 1 (P<0.01) and 5 (P<0.05), but not at day 0. CONCLUSIONS: Our findings show that autonomic imbalance, already evident on the day of the acute event, progresses further over the next 24 h and recovers over the next few days. Low heart rate variability as early as 24 h after acute MI may be a useful predictor of cardiac mortality and contribute to the early risk stratification and therapeutic management of patients.

The effect of short-term depressive episodes on the risk stratification of acute coronary syndromes: a case-control study in Greece (Cardio 2000).

OBJECTIVE: The aim of this study is to evaluate the effect of recent depressive episodes on coronary risk, taking into account the presence of several cardiovascular risk factors and various lifestyles, and social conditions that aggregate in the Greek population. METHODS AND RESULTS: CARDIO2000 is a matched case-control study consisting of 750 patients with a first event of acute coronary syndrome and 778 cardiovascular disease-free hospitalized subjects, randomly and stratified selected from several Greek regions. Assessment of depressive symptoms, during the past month, was based on the CES-D Scale (Radloff S, 1977). 158 (21%) coronary patients and 74 (9%) controls had short-term depressive symptoms (P<0.001). A recent depressive episode increases coronary risk by 12%, after adjusting for several confounders, while the previous outcome seems to differ significantly between sexes (OR-men = 1.09 vs. OR-women = 1.19, P<0.01). The effect of the interaction between depression and various components of social class (education, occupation, income) increases the coronary risk from 55% to 132%, while the interaction with marital status increases the previous risk by 167%, in divorced/widowed men, and by 123%, in women. Also, significant additive effects were observed between depression and smoking (25% increased coronary risk per pack-year), alcohol consumption (+97%), physical inactivity (+137%) and obesity (+127%). CONCLUSION: This study showed the moderate effect of recent depression on the risk of developing non-fatal acute coronary syndromes in the investigated population. Also, sex differences and the additional effect of the interactions between short-term depressive episodes and several emerging or established cardiovascular risk factors occurred.

Closed relation between carotid and ascending aortic atherosclerosis in cardiac patients.

BACKGROUND: Carotid atherosclerosis and aortic atherosclerosis are both associated with coronary artery disease and cerebral thromboembolism. However, the relationship between asymptomatic carotid and aortic atherosclerosis is not well known. METHODS AND RESULTS: Sixty-two consecutive cardiac patients (mean age 57 years) without a history of atherosclerotic cardiovascular disease who were referred for transesophageal echocardiography were included. By means of a high-resolution ultrasound technique, normal carotid arteries were found in 12 patients (19.4%), whereas 15 patients (24. 2%) had increased intima-media thickness, and the remaining 35 patients (56.5%) had atherosclerotic plaques (intima-media thickness >/=1.3 mm). Transesophageal echocardiography characterized ascending aortic intimal morphology as normal in 1 patient (1.6%), as thickening in 22 patients (35.5%), and as atherosclerotic plaques in 39 patients (62.9%). Patients with both carotid and aortic plaques were older compared with patients without plaques; also, a higher percentage of patients with carotid and aortic plaques suffered from hypertension and diabetes mellitus compared with patients without plaques (P:<0.001). The incidence of carotid plaques was 74.3% (29 of 39 patients) in the subgroup with aortic plaques; there was a stepwise increase in the percentage of patients with carotid plaques among the patients with increasing grades of aortic atherosclerosis. Furthermore, the incidence of ascending aortic plaques was 82.8% (29 of 35 patients) in the subgroup with carotid plaques. Regression analysis revealed that age and carotid plaques were independently related to the presence of aortic plaques. In the entire study population, the presence of carotid plaques had a high positive predictive value (83%), an acceptable sensitivity (75%) and specificity (74%), and a relatively low negative predictive value (63%) for the presence of aortic plaques. CONCLUSIONS: In cardiac patients without clinical evidence of atherosclerotic cardiovascular disease, a high prevalence of combined aortic and carotid plaques were detected. The presence of carotid plaque reflects the presence of aortic plaque, whereas the absence of carotid plaque may not reflect the absence of aortic plaque.

Microalbuminuria is associated with abnormal thoracic aortic mechanics in essential hypertension.

In a population of 162 patients with currently untreated essential hypertension, those with microalbuminuria (n = 75) had significantly impaired elastic properties of the proximal ascending thoracic aorta compared with their normoalbuminuric counterparts (n = 87), whereas urinary albumin excretion was a significant predictor of aortic mechanics in the entire population. Impaired aortic mechanics in microalbuminuric hypertensives were not fully accounted for by clustering of classic risk factors for atherosclerosis, and constitute a finding that may entail additional long-term cardiovascular risk in this subgroup of patients.

Retrograde nontransseptal balloon mitral valvuloplasty by the brachial artery approach.

Retrograde nontransseptal balloon mitral valvuloplasty is a purely transarterial technique for percutaneous treatment of mitral stenosis. We report the first use of this technique via the brachial artery for a patient with aortoiliac atherosclerosis, and we comment on the difficulties and perspectives of this approach.

Mild left ventricular hypertrophy in essential hypertension: is it really arrhythmogenic?

Left ventricular hypertrophy (LVH) has been associated with an increased incidence of ventricular arrhythmias and sudden cardiac death in hypertensive patients. However, it is not known whether this relationship exists in early asymptomatic hypertensives with mild LVH. We prospectively examined 100 consecutive patients with essential hypertension, 35 without and 65 with mild LVH on echocardiography. All underwent a detailed noninvasive arrhythmia work-up and were subsequently followed-up for 3 +/- 1 years in an ambulatory hypertension clinic. None of the 12-lead electrocardiographic parameters examined differed between the two hypertensive groups. A similarly low incidence of simple forms of ventricular ectopy was present in both groups, whereas complex forms of ventricular ectopy were extremely rare in either group. The signal-averaged electrocardiographic parameters examined were also not significantly affected by the presence of mild LVH. Arrhythmia-related symptoms or malignant ventricular arrhythmia events were not observed in either group of patients during follow-up with antihypertensive treatment. The latter resulted in LVH regression in the 65 patients with mild LVH at baseline. It appears that mild LVH among ambulatory hypertensive patients does not carry an additive arrhythmogenic risk and can be successfully reversed with the appropriate antihypertensive therapy, with no need of additional antiarrhythmic management.

The role of carotid atherosclerosis in the distinction between ischaemic and non-ischaemic cardiomyopathy.

AIM: Sometimes ischaemic cardiomyopathy is a result of severe coronary artery disease of an occult course, without typical symptoms or evidence of myocardial infarction. This form of presentation is usually indistinguishable from non-ischaemic dilated cardiomyopathy. Carotid bifurcation atherosclerosis and coronary artery disease have been shown to be strongly associated. We prospectively examined the value of extracranial carotid atherosclerosis in the distinction between ischaemic and non-ischaemic aetiology in patients with clinically unexplained cardiomyopathy. METHODS AND RESULTS: Seventy-eight patients with undetermined dilatation and diffuse impairment of the left ventricular contraction were studied within 28 months. They underwent carotid scan and coronary arteriography. Carotid atherosclerosis was found to be very common in ischaemic and rare in non-ischaemic cardiomyopathy. The presence of at least one abnormal carotid finding (intima-media thickness >1 mm, plaques, severe carotid stenosis) was 96% sensitive and 89% specific for ischaemic cardiomyopathy. CONCLUSION: Carotid scanning may be a useful screening and decision making tool in patients with cardiomyopathy of indecisive cause. Patients with carotid atherosclerosis are likely to suffer from severe coronary artery disease. Coronary angiography and subsequent myocardial viability studies, when indicated, could be considered early during their evaluation. In contrast, a negative carotid scan predicts non-ischaemic cardiomyopathy.

Prevalence of autoantibodies against contractile proteins in coronary artery disease and their clinical implications.

In this initial study, we found that autoantibodies against actin and myosin were present during and after an acute coronary syndrome. Moreover, they correlated with persistent troponin-I elevation at follow-up, and with late myocardial infarction.

Subpectoral cardioverter-defibrillator implantation using a lateral approach.

INTRODUCTION: Third-generation cardioverter-defibrillators have revolutionized management of ventricular tachyarrhythmias. Implantation can be performed in the electro-physiology laboratory, with minimal morbidity. Generator size has shrunk to the point that subcutaneous implantation is feasible and safe, even under local anesthesia. The prepectoral technique, however, is associated with increased mechanical stress to the subcutaneous tissue and can predispose to device erosion or infection. These complications may be avoided by submuscular placement. Among subpectoral techniques, the lateral approach offers unrestricted ability to deploy patches or array electrodes, should the need arise, and may represent the optimal implant technique under some circumstances. METHODS: We studied 29 male patients, aged 29-78 years, who presented with syncope or sustained ventricular tachycardia, and underwent subpectoral defibrillator implantation under general anesthesia or conscious sedation. All devices were third-generation active can systems with biphasic shock capability. Six dual-chamber defibrillators were used. RESULTS: Subpectoral implantation was successful in all cases, with an estimated blood loss of 28+/-17 mL and no immediate complications. Except for one patient who developed twiddler's syndrome and ultimately required revision to a subcutaneous pocket, the implant site was tolerated well, and no limitation in the range of motion of the upper limb was observed during 20 months of follow-up. CONCLUSIONS: Subpectoral implantation using a lateral approach is technically straightforward and can be applied globally, with modest additional resource and equipment requirements. Familiarity with this approach can maximize the likelihood of successful defibrillator implantation in the electrophysiology laboratory.

Effects of ischemia on P wave dispersion and maximum P wave duration during spontaneous anginal episodes.

P wave dispersion (P dispersion), defined as the difference between the maximum and the minimum P wave duration, and maximum P wave duration (P maximum) are electrocardiographic (ECG) markers that have been used to evaluate the discontinuous propagation of sinus impulses and the prolongation of atrial conduction time, respectively. To study the effects of myocardial ischemia on P dispersion and P maximum, 95 patients with coronary artery disease (CAD) and typical angina pectoris and 15 controls with angina like symptoms underwent 12-lead surface ECG during and after the relief of pain. During pain and during the asymptomatic period, P maximum and P dispersion were calculated from the averaged complexes of all 12 leads. P dispersion increased significantly during spontaneous angina (45+/-17 ms) compared to the asymptomatic period (40+/-15 ms), P < 0.001 only in the patient group. Both P maximum and P dispersion showed higher values during angina in those patients who developed diffuse ischemia, as estimated with ST segment changes in multiple ECG leads. P dispersion showed higher values during the anginal episode in patients with left ventricular dysfunction, independently of the presence of a previous myocardial infarction. Atrial conduction abnormalities, as estimated with P maximum and particularly P dispersion, are significantly influenced by myocardial ischemia in patients with CAD and spontaneous angina.

Significance of exercise-induced simultaneous ST-segment changes in lead aVR and V5.

This study was undertaken to investigate the ability of the exercise-induced ST depression in lead V5 and concomitant ST elevation in lead aVR for the identification of the significantly narrowed coronary artery in patients with single vessel disease. We studied 229 consecutive patients who developed the aforementioned exercise-induced electrocardiographic changes. All underwent Thallium-201 scintigraphy and coronary arteriography. Patients were divided into three groups. In group A, 58 patients with ST depression in V5 and ST elevation in aVR, in group B 149 patients with ST depression in V5 without ST elevation in aVR, and in group C 22 patients with ST elevation in aVR without ST depression in V5 induced with exercise, were included. In group A, 81% of the patients while in group B, 29% and in group C only 18% of the patients had left anterior descending artery disease. According to Thallium-201 scintigraphy, 80% of the group A, 27% of the group B and 12% of the group C patients developed myocardial ischemia in areas supplied by the left anterior descending artery. Thus, exercise-induced ST depression in V5 and concomitant ST elevation in aVR, may detect left anterior descending artery significant stenosis in patients with single vessel disease.

QRS prolongation on the signal-averaged electrocardiogram versus ST-segment changes on the 12-lead electrocardiogram: which is the most sensitive electrocardiographic marker of myocardial ischemia?

BACKGROUND: ST-segment changes and QRS prolongation are electrocardiographic (ECG) markers of myocardial ischemia. HYPOTHESIS: This study was undertaken to investigate the appearance of QRS duration changes with or without concomitant ST-segment changes during a typical anginal episode. METHODS: For this purpose, 126 patients underwent 12-lead surface ECG and signal-averaged electrocardiogram (SAECG) during typical anginal pain as well as at the time the patient was asymptomatic. In both periods, QRS duration and ST-segment changes were evaluated. All patients underwent cardiac catheterization. RESULTS: Of the 126 patients, 108 (86%) had coronary artery disease (CAD), whereas the remaining 18 (14%) patients had normal coronary arteriograms. During typical anginal pain, 75 of the 108 (70%) patients with CAD and 2 of the 18 (11%) patients with normal coronary arteriograms developed QRS prolongation, whereas 60 of the 108 (56%) patients with CAD and 2 of the 18 (11%) patients with normal coronary vessels developed ST-segment changes. Thus, the sensitivities of QRS prolongation measured by SAECG and of ST-segment changes on the surface ECG for the detection of myocardial ischemia were found to be 70 and 56%, respectively, (p < 0.01), whereas the specificities were both found to be 89% (p = NS). CONCLUSIONS: During typical anginal pain, QRS prolongation on the SAECG is more sensitive than are ST-segment changes on the ECG for the detection of myocardial ischemia.