Abstract: This study investigated plasma brain natriuretic peptide (BNP) levels in normotensive and hypertensive patients with suspected coronary artery disease during radionuclide pharmacological stress testing. Twenty-seven normotensive patients (15 males, aged 63.0+/-4.5 years and 12 females, aged 63.0+/-4.1 years) and 38 essential hypertensive patients (25 males, aged 63.3+/-3.3 years and 13 females, aged 64.6+/-2.6 years) with chest pain and exercise stress testing inconclusive for coronary artery disease underwent myocardial perfusion single-photon emission computed tomography (SPECT) using adenosine infusion. SPECT identified patients without (16 normotensive and 22 hypertensive) and patients with (11 normotensive and 16 hypertensive) transient perfusion defects. Basal BNP levels in normotensive patients without transient myocardial ischemia (3.1+/-1.2 fmol/ml) were significantly (P<0.01) lower than those observed in normotensive patients with transient ischemia (8.2+/-1.2 fmol/ml), whereas BNP levels in hypertensive patients without transient ischemia (8.2+/-1.0 fmol/ml) did not significantly differ from those in hypertensive patients with transient ischemia (8.1+/-2.0 fmol/ml). No significant difference was found in BNP levels between males or females either in normotensive or hypertensive patients without or with ischemia. Adenosine infusion did not significantly change BNP levels in any subject group without or with myocardial perfusion defects. Our findings show that increases in BNP allow early detection of myocardial ischemia in normotensive patients, but not in hypertensive patients with suspected coronary artery disease. Adenosine-induced myocardial ischemia does not affect BNP production already activated by coronary artery disease in normotensive patients and by hemodynamic changes in hypertensive patients.

Abstract: BACKGROUND: We describe the clinical characteristics, treatments and in-hospital case-fatality rates in an unselected population of patients admitted for acute myocardial infarction. METHODS: From January 2000 to June 2007, we tracked consecutive patients who were admitted to 7 tertiary referral and 21 county hospitals in Romania for medical treatment of ST-segment elevation acute myocardial infarction. These patients were enrolled in the Romanian Registry for ST-segment Elevation Myocardial Infarction. For this prospective study, we collected data on demographic characteristics, cardiovascular risk factors, various aspects of treatment for myocardial infarction, and in-hospital death. RESULTS: The 9186 patients in the study group had a mean age of 63.8 years. The median time from onset of symptoms to thrombolysis was 230 (interquartile range 120-510) minutes. Of the 9186 patients, 4986 (54.3%) had hypertension, 1974 (21.5%) had diabetes mellitus, 3545 (38.6%) had lipid disorders and 4653 (50.7%) were smokers. The in-hospital mortality rate was 12.7% (1170 deaths). The study group consisted of 2893 women and 6293 men. The women were older than the men and had higher rates of hypertension and diabetes mellitus but were less likely to be smokers. A smaller proportion of women than men presented within 2 hours after onset of symptoms (23.1% v. 34.4%, p < 0.001). Smaller proportions of women received thrombolytics (40.8% v. 53.5%, p < 0.001), anticoagulants (93.4% v. 95.2%; p = 0.001), antiplatelet agents (88.3% v. 91.2%, p < 0.001) and primary percutaneous coronary interventions (1.5% v. 2.2%, p = 0.030). The risk of in-hospital death was greater for women, even after adjustment for confounders (odds ratio 1.33, 95% confidence interval 1.13-1.56; p < 0.001). INTERPRETATION: The rates of reperfusion therapy for patients with acute myocardial infarction were low, and in-hospital case-fatality rates were high in this study. Excess in-hospital mortality was more pronounced among women.

Abstract: AIMS: We investigated the relationship between autonomic nervous system balance, systemic immune activation, endothelial dysfunction, and depression in patients free of coronary heart disease (CHD) with increased CHD risk. METHODS AND RESULTS: Depression status (Beck Depression Inventory, BDI), selected CHD risk factors, inflammation markers, measures of heart rate variability (HRV), and indices of endothelial function (flow-mediated dilation, FMD) were evaluated in 415 subjects free of CHD, diabetes mellitus, and other life-threatening conditions, with at least two CHD risk factors among the following: older age, male gender, current smoking, hypertension, and dislipidaemia. Overall, 51.7% of the participants were males, aged 57.6 +/- 8.8 years on average (minimum 30, maximum 70). Almost half were hypertensive, 43.9% were dyslipidemic, 30.4% current smokers, and 23.1% showed a depressive symptomatology (BDI > or = 10). Logistic regression showed that, as compared with non-depressed individuals and after adjustment for age, gender, and hypertension, depressive subjects were significantly more likely to be smokers, to have higher total cholesterol, higher C-reactive protein, and Interleukin-6. In addition, depressed subjects were more likely to have altered HRV and their FMD was severely impaired (adjusted odds ratio of 1% increase = 0.72; 95% CI: 0.61-0.86). CONCLUSION: Our data indicate an independent association between depression and impaired HRV, systemic inflammatory, and endothelial function. These mechanisms play a role not only in the complication of advanced forms of disease, but also promote and/or accelerate the early disease and connect depression and CHD.

Abstract: BACKGROUND: Diagnosis costs for cardiovascular disease waste a large amount of healthcare resources. The aim of the study is to evaluate the clinical and economic outcomes of alternative diagnostic strategies in low risk chest pain patients. METHODS: We evaluated direct and indirect downstream costs of 6 strategies: coronary angiography (CA) after positive troponin I or T (cTn-I or cTnT) (strategy 1); after positive exercise electrocardiography (ex-ECG) (strategy 2); after positive exercise echocardiography (ex-Echo) (strategy 3); after positive pharmacologic stress echocardiography (PhSE) (strategy 4); after positive myocardial exercise stress single-photon emission computed tomography with technetium Tc 99m sestamibi (ex-SPECT-Tc) (strategy 5) and direct CA (strategy 6). RESULTS: The predictive accuracy in correctly identifying the patients was 83,1% for cTn-I, 87% for cTn-T, 85,1% for ex-ECG, 93,4% for ex-Echo, 98,5% for PhSE, 89,4% for ex-SPECT-Tc and 18,7% for CA. The cost per patient correctly identified results $2.051 for cTn-I, $2.086 for cTn-T, $1.890 for ex-ECG, $803 for ex-Echo, $533 for PhSE, $1.521 for ex-SPECT-Tc ($1.634 including cost of extra risk of cancer) and $29.673 for CA ($29.999 including cost of extra risk of cancer). The average relative cost-effectiveness of cardiac imaging compared with the PhSE equal to 1 (as a cost comparator), the relative cost of ex-Echo is 1.5x, of a ex-SPECT-Tc is 3.1x, of a ex-ECG is 3.5x, of cTnI is x3.8, of cTnT is x3.9 and of a CA is 56.3x. CONCLUSION: Stress echocardiography based strategies are cost-effective versus alternative imaging strategies and the risk and cost of radiation exposure is void.

Abstract: Little is known about changes in myocardial perfusion of myocardial regions supplied by angiographically normal or near-normal coronary arteries after percutaneous coronary intervention (PCI) of the target lesion. The purpose of this study was to assess the effect of PCI on coronary blood flow at rest in sites remote from the PCI. We studied 85 patients who underwent successful elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction frame count to provide a simple continuous index of coronary flow and myocardial perfusion in the target and nontarget arteries. Coronary artery diameters of nontarget vessels did not significantly differ before and after PCI and at 6 months' follow-up. At baseline, the greater the percent diameter stenosis in the target artery, the slower the flow in the target (r = 0.22, p <0.01) and nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not account for simultaneous changes in epicardial coronary blood flow of the nontarget artery. After 6 months, coronary blood flow improved in both the target (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided evidence of a functional link between coronary blood flow in diseased and nondiseased arteries. Relief of a significant stenosis using PCI globally improved regional and global myocardial blood flow at rest in patients with stable angina. Flow improvement was not apparent at the time of revascularization, but at 6 months' follow-up. Late upturn of the microcirculation may account for delayed recovery of myocardial perfusion.

Abstract: BACKGROUND: Vagal fibres are distributed both in the perivascular connective tissue and in the adventitia around the circumference of arteries, and contribute to coronary artery dilation. The aim of the manuscript is to examine whether morphologic changes of the vessel wall due to the atherosclerotic process might be associated with autonomic nervous system dysfunction. METHODS AND RESULTS: We studied 42 patients with single vessel disease referred for percutaneous coronary revascularization. Patients underwent intravascular ultrasound at the site of the ischemia-related artery before intervention. The autonomic nervous system activity was assessed by the analysis of heart rate variability (HRV) in the frequency domain. The high frequencies (HF) are predominantly under the influence of the parasympathetic system, while the low/high frequency (LF/HF) ratio represents an index of sympatho-vagal balance. Plaque plus media cross-sectional area was inversely related to HF components (r=-0.34, p<0.05), and directly related to LF/HF ratio (r=0.38, p<0.05). Patients with expansive remodeling showed lower HF values (0.07+/-0.06 nu versus 0.14+/-0.09 nu, p<0.01) and higher LH/HF ratio (2.1+/-1.1 versus 1.4+/-1.1; p<0.05). LF changes were independent of any morphologic features. On multivariate analyses the remodeling index was the only independent determinant of HF and LF/HF ratio. CONCLUSIONS: Outward stretch of the vessel wall behind the plaque, as a consequence of increasing plaque size and expansive arterial remodeling is associated to autonomic dysfunction namely due to impairment of the vagal tone. It is unknown if remodeling is a cause of vagal impairment or if vagal impairment may contribute to arterial remodeling.

Abstract: OBJECTIVE: Patients undergoing radiologic and nuclear medicine examination often receive little, if any, information related to the radiologic dose and consequent potential long-term cancer risk. This "economical with the truth" communication may violate basic patients' rights. We assessed the information perceived by patients on the radiation dose exposure during nuclear medicine examinations. METHODS: We recruited 109 consecutive patients (66 male; aged 66 +/- 10 years) who were referred to the Nuclear Medicine laboratory of Sant'Orsola-Malpighi Hospital (Bologna University, Bologna, Italy) for a cardiac rest-stress technetium-99m sestamibi scan. This scan gives an effective dose of approximately 10 mSv, corresponding to a dose equivalent of 500 chest x-rays (European Commission Medical Imaging Guidelines 2001) and an estimated extra lifetime attributable risk of 1 cancer in 1,000 exposed subjects (Biological Effects of Ionizing Radiation VII Committee 2005). RESULTS: Radiation dose exposure was correctly identified by 21% of patients, with the remaining 79% underestimating the exposure by at least 500 times, considered to be zero by 11%, one-half of a chest x-ray by 23%, 1 chest x-ray by 35%, and "don't know" by 10%. The long-term cancer risk was correctly estimated by 27% of patients, with the remaining substantially underestimating the risk, considered to be "zero" by 30%, 1 in 1 million by 19%, 1 in 100,000 by 9%, and "don't know" by 10%. CONCLUSION: Patients undergoing common cardiac stress scintigraphy examinations involving significant radiation exposure have little or no awareness about nuclear medicine dose (and corresponding risk). This ineffective communication poses significant ethical concerns and possible vulnerability to legal suits against practitioners and prescribers, especially in case of inappropriate examinations.

Abstract: BACKGROUND: High-dose glucose-insulin-potassium (GIK) solution has beneficial effects on reducing mortality in acute myocardial infarction. Dipyridamole (DIP) is a powerful antioxidant and increases adenosine concentration. Experimentally, GIK and DIP have additive protective effects in ischemia-reperfusion injury. AIM: This work aims to assess the acute effects of DIP alone, GIK alone, and GIK+DIP on left ventricular function in patients evaluated early after an acute myocardial infarction. METHODS: Ten male patients (age 63+/-11 years) with uncomplicated acute myocardial infarction were evaluated within 3 days after admission. All had been treated with systemic thrombolysis and were on full therapy (including beta-blockers) at the time of testing. They underwent stress echocardiography [2D echo, with wall motion score index (WMSI) evaluated in a 16-segment model of the left ventricle, with each segment scored from 1=normal to 4=dyskinetic] during low-dose DIP alone (0.28 mg/kg in 4 min); GIK alone (4-h infusion of glucose 30%, 25 insulin units, and 40 mEq of KCl, at an infusion rate of 1.5 ml/kg/h); and GIK+DIP. RESULTS: Regional systolic function (baseline WMSI=1.69+/-0.2) improved after DIP (1.54+/-0.1), GIK (1.54+/-0.1), and, to a greater extent, after GIK+DIP (1.33+/-0.2; p<0.001 vs. baseline; p<0.05 vs. DIP; p<0.05 vs. GIK). CONCLUSION: High-dose GIK has an acute beneficial effect on regional left ventricular function in patients with acute myocardial infarction. This beneficial effect is potentiated by low-dose DIP coadministration.

Abstract: AIMS: Cardio-cardiac reflexes may be evoked by both myocardial ischaemia and coronary occlusion itself. The aim of the study was to assess the intrapatient behaviour of autonomic nervous system balance during spontaneous and balloon-induced coronary ischaemia. METHODS AND RESULTS: We studied a group of patients admitted to the coronary care unit for acute coronary syndrome without ST-segment elevation who experienced spontaneous episodes of myocardial ischaemia during bed rest and ECG monitoring. The inclusion criterion was 80-90% lumen stenosis, amenable to angioplasty. Balloon coronary occlusion was performed at 4-6 atmospheres for 120 s. Autonomic nervous system activity was assessed by heart rate variability (HRV) analysis in frequency domain. We analysed 14 episodes of spontaneous ischaemia and 14 episodes of balloon coronary occlusion. During spontaneous ischaemia, HRV showed an increase in the low/high frequencies ratio (11.8 +/- 5.7), as compared to 5 min before and 5 min after (4.4 +/- 2.7 and 3.9 +/- 1.8, respectively) (p = 0.001). The opposite occurred during balloon coronary occlusion (0.8 +/- 0.4 vs. 3.9 +/- 2.0 and 5.1 +/- 2.1, respectively; p = 0.001). CONCLUSIONS: Balloon inflation and occlusion evokes baroreceptor vagal predominance in response to a stretch stimulus of the coronary artery. Conversely, spontaneous occlusion during unstable angina is accompanied by naturally occurring sympathetic activation. Sympathetic activation may have a role in the natural history of the disease.

Abstract: We studied the effect of pravastatin on coronary perfusion after percutaneous transluminal coronary angioplasty. An exercise test performed within 2 weeks after percutaneous transluminal coronary angioplasty induced reversible perfusion defects in 66% of patients taking pravastatin and 64% of those taking placebo. At follow-up, the exercise test still induced reversible perfusion defects in 3% of patients taking pravastatin and 29% of those taking placebo.

Abstract: BACKGROUND: The prognosis for women with chest pain and angiographically normal coronary arteries is believed to be totally benign. Previous studies, however, did not account for the delay of a decade or so in the development of coronary artery disease that women may experience. METHODS AND RESULTS: This study assessed long-term follow-up of 42 women with de novo angina, evidence of reversible myocardial perfusion defects on SPECT, and normal coronary angiograms. At recruitment, all women underwent endothelial function testing (intracoronary acetylcholine) during catheterization. Patients were followed up for >10 years. Angiography was repeated at the end of the follow-up in 37 patients. At recruitment, 22 patients developed diffuse vasoconstriction during acetylcholine in the absence of identifiable focal coronary spasm (acetylcholine-positive group). The remaining 20 patients showed vasodilation (acetylcholine-negative group). At the end of follow-up, in the acetylcholine-positive group, 1 patient developed cardiac death, 13 still complained of chest pain, and 8 had remission of symptoms. In the acetylcholine-negative group, all patients showed complete resolution of chest pain beginning 6 to 36 months after baseline assessment. Angiography showed development of coronary artery disease in the 13 symptomatic patients in the acetylcholine-positive group. CONCLUSIONS: In women with angiographically normal-appearing coronary arteries, persistence of chest pain over the years often relates to development of coronary artery disease. Endothelial dysfunction in a setting of normal coronary arteries is a sign of future development of atherosclerosis.

Abstract: OBJECTIVE: To assess the relation between markers of inflammation and the presence of multiple vulnerable plaques in patients with non-ST segment elevation acute coronary syndromes. DESIGN: Prospective cohort study of 55 patients with non-ST segment elevation acute coronary syndromes and angiographically documented coronary disease. Blood samples were obtained at study entry for the assessment of high sensitivity C reactive protein (CRP), neopterin, and neutrophil count. Coronary stenoses were assessed by quantitative computerised angiography and classified as "complex" (irregular borders, ulceration, or filling defects) or "smooth" (absence of complex features). Extent of disease was also assessed by a validated angiographic score. RESULTS: Neutrophil count (r = 0.36, p = 0.007), CRP concentration (r = 0.33, p = 0.02), and neopterin concentration (r = 0.45, p < 0.001) correlated with the number of complex stenoses. Patients with multiple (three or more) complex stenoses, but not patients with multiple smooth lesions, had a higher neutrophil count (5.9 (1.4) x 10(9)/l v 4.8 (1.4) x 10(9)/l, p = 0.02), CRP concentration (log transformed) (1.08 (0.63) v 0.6 (0.6), p = 0.03), and neopterin concentration (log transformed) (0.94 (0.18) v 0.79 (0.15), p = 0.002). Multiple regression analysis showed that neopterin concentration (B = 4.8, 95% confidence interval (CI) 1.9 to 7.7, p = 0.002) and extent of coronary artery disease (B = 0.6, 95% CI 0.03 to 1.2, p = 0.04) were independently associated with the number of complex stenoses. CONCLUSIONS: Acute inflammatory markers such as high neutrophil count, CRP concentration, and neopterin concentration correlate with the presence of multiple angiographically complex coronary stenoses. Neopterin concentration was a stronger predictor of multiple complex plaques than were neutrophil count and CRP concentration. These findings suggest that a relation exists between inflammation and pancoronary plaque vulnerability.

Abstract: BACKGROUND: Morbidity of patients with Syndrome X (SX; chest pain and normal coronary angiograms) is high and is associated with continuing episodes of chest pain and hospitalization. Impairment of microvascular endothelial function caused by increased oxidative stress has been suggested to be a mechanism of the disease. Superoxide dismutase (SOD) is the major antioxidant enzyme system of the vascular wall. This study sought to establish whether combination treatment with ACE inhibitors and statins reduces oxidative stress and improves quality of life of patients with cardiac SX. METHODS AND RESULTS: Forty-five patients with SX were randomly assigned to receive either a combination of ramipril (10 mg/d) and atorvastatin (40 mg/d) or placebo for 6 months. We determined the activity of extracellular SOD and its relation to flow-dependent endothelium-mediated dilation (FMD) and quality of life (exercise capacity and score with Seattle Angina Questionnaire [SAQ]) before and after treatment. After 6 months, patients with SX who received atorvastatin and ramipril had significantly reduced (P=0.001) SOD levels (188.1+/-29.6 U/mL). No significant changes were seen on placebo (262.9+/-48.8 U/mL). Reduction of SOD after therapy was negatively correlated with FMD (r=0.38; P=0.01) and positively with total cholesterol (r=-0.56; P<0.001). At follow-up, patients taking atorvastatin and ramipril improved their quality of life both in terms of exercise duration (by 23.46%) and SAQ (by 64.1%). CONCLUSIONS: Six months of therapy with atorvastatin and ramipril improves endothelial function and quality of life of patients with SX. Reduced SOD activity may reflect low superoxide anion production. Benefits of these drugs may be related to reduction of oxidative stress.

Abstract: AIMS: We sought to assess (1) whether C-reactive protein (CRP) is an independent predictor of future cardiovascular events after adjustment for coronary artery disease (CAD) severity and (2) whether CRP levels correlate with number of angiographically complex coronary artery stenosis. METHODS AND RESULTS: We studied 825 consecutive angina patients (mean age 63+/-10 years, 74% men), 700 with chronic stable angina (CSA) and 125 with acute coronary syndromes without ST-segment elevation (ACS). The composite endpoint of non-fatal acute myocardial infarction, hospital admission with class IIIb unstable angina and cardiac death was assessed at one year follow-up. Hs-CRP level was higher in CSA patients with the combined end-point (P=0.03) after adjustment for number of diseased coronary arteries. Hs-CRP was also significantly higher in patients with ACS compared to CSA ( P=0.004) and correlated with number of complex angiographic stenoses (r=0.36, P=0.01). Hs-CRP was also increased in patients with NYHA functional class III or IV compared to those in class I or II (p<0.0001). CONCLUSIONS: CRP levels predict future cardiovascular events independently of CAD severity and correlate with number of angiographically complex coronary artery stenosis in patients with ACS. Thus, CRP levels are a marker of atheromatous plaque vulnerability and CAD activity.

Abstract: OBJECTIVES: We sought to investigate the relationship among C-reactive protein (hs-CRP), clinical characteristics, exercise stress test responses, and ST-segment changes during daily life in patients with typical chest pain and normal coronary angiograms (CPNCA). BACKGROUND: Patients with CPNCA have coronary microvascular endothelial dysfunction and myocardial ischemia. Elevated hs-CRP levels have been related to atherogenesis and endothelial dysfunction. The relationship between hs-CRP and disease activity has not been previously investigated in CPNCA patients. METHODS: We studied 137 consecutive CPNCA patients (mean age, 57 +/- 9; 33 men). All completed standardized angina questionnaires, underwent exercise stress testing, 24-h ambulatory electrocardiogram (ECG) monitoring (Holter), and hs-CRP measurements at study entry. RESULTS: C-reactive protein levels (mg/l) were higher in patients with frequent (2.9 +/- 3.3) and prolonged (3.9 +/- 4.1) chest pain episodes, and in those with ST-segment depression on exercise testing (2.6 +/- 2.8) and Holter monitoring (3.4 +/- 3.1) compared with patients with occasional (1.3 +/- 1.2; p = 0.002) or shorter chest pain (1.5 +/- 1.3; p < 0.001) episodes, negative exercise stress testing (1.1 +/- 1.1; p < 0.001), and no ST-segment shifts on Holter monitoring (0.9 +/- 0.7; p < 0.001). Moreover, we found a correlation between hs-CRP concentration and number of ischemic episodes during Holter monitoring (r = 0.65; p < 0.001) and with the magnitude of ST-segment depression on exercise testing (r = -0.43; p < 0.001). The hs-CRP was the only independent variable (multivariate logistic regression) capable of predicting positive findings on Holter monitoring (odds ratio [OR], 3.8; confidence interval [CI], 2.3 to 6.2) and exercise testing (OR, 1.7; CI, 1.2 to 2.2). CONCLUSIONS: The hs-CRP correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.

Abstract: AIM: Previous animal studies suggested that vagal tone contributes to tonic dilatation of coronary arteries. We hypothesized that low parasympathetic activity might be among the causes of coronary instability in the setting of acute coronary syndrome without ST-segment elevation. METHODS AND RESULTS: We studied 172 consecutive patients. Vagal and sympathetic activities were assessed by time domain measures of heart rate variability. PNN50 <3% was used as a marker of low parasympathetic activity. At 6-month follow-up 32 patients developed coronary events. Coronary events were lower during hospitalization (n=9) than during follow-up (n=23). Extremely low values of parasympathetic activity (pNN50 <3%) were strongly related to subsequent events (P<0.001). PNN50 <3% was found in 56% of patients having adverse events versus 5% of patients who had good outcome. Among patients who had pNN50 <3%, 18 patients (72%) had subsequent coronary events vs seven patients (28%) who had a good outcome. CONCLUSIONS: These data show that in acute coronary syndrome without ST-segment elevation, a significant number of patients developing subsequent coronary events have a loss of vagal tone. Simple electrocardiographic variables, as pNN50 <3%, may be of great clinical value in identifying patients at high risk of subsequent coronary events even after apparent clinical stabilization.

Abstract: Cardiotoxicity manifesting as myocardial ischemia is not generally recognized as a side effect of amphetamine use or abuse. However, at least 9 cases have been reported since 1987. In this report a case of acute myocardial infarction due to oral amphetamine therapy is presented. The patient was treated with thrombolytic therapy but there were no signs of reperfusion. His coronary cine-angiograms were normal. The literature regarding amphetamine use or abuse is also reviewed, and the possible mechanisms of this pathology are analyzed.

Abstract: In this epidemiological study we have studied during 1997 in Emilia-Romagna (population about four million) Italy, mortality from ischaemic heart disease, hypertension, cerebrovascular and respiratory disease in 50-89 year-olds. The data were collected from "Ufficio Risorse Informative" and "servizio Meteorologico" of the Emilia-Romagna region. The results show high indices of deaths in the elderly, the highest being those of the 80-89 year-olds, during the winter with a maximum in January. There were some differences between males and females with regard to cold-related mortality of the different diseases. Comparing mortality rates of persons living in the North (Piacenza) and in the South (Rimini) of Emilia-Romagna, a consistent lower mortality was found in the people of Rimini. These results confirm the close relationship between advanced age, cold and excess mortality in Emilia-Romagna. The results suggest that at least two factors may be involved in explaining excess winter mortality: the sympathetic system changes in the elderly and the effects of cold on some haemostatic factors.

Abstract: A 70-year-old man with a Duromedics mitral valve prosthesis had two episodes of infective endocarditis caused by enterococcus (1994 and 1996). Colonoscopy revealed five polyps. Surgical resection was performed and 2 days later the patient had dyspnea and fever. Because of a suspected valve thrombosis, intravenous heparin was given which resulted in hematic effusion in the Douglas' cul-de-sac. Intravenous heparin was withdrawn but the patient continued to have a worsening dyspnea, hyperthermia and hypotension. The patient was transferred to our Institution in cardiogenic shock. Acute thrombosis of the valve was diagnosed by echocardiography, and the patient died before transesophageal Doppler echocardiography was performed. Post mortem examination revealed mitral valve infective thrombosis. In patients with valvular prostheses, endocarditis is an added thromboembolic risk.

Abstract: The aim of this study was to analyze the very early (first 24 hours) effect of successful or failed thrombolytic therapy on the autonomic nervous system. Thirty consecutive patients with a first acute myocardial infarction were enrolled in the study, and admitted to the Coronary Care Unit within 6 hours of the onset of symptoms and treated with systemic thrombolytic therapy. All patients underwent 24-hour Holter monitoring in order to analyze ST segment variation. The autonomic nervous system was evaluated by frequency-domain heart rate variability: low frequency/high frequency ratio (LF/HF) was measured at the beginning of Holter monitoring (T1), 15 min after reperfusion or 1 hour from the start of thrombolytic therapy (T2) and after 24 hours (T3). Reperfusion status was assessed by a > or = 50% reduction in ST segment elevation within 90 min of thrombolytic therapy, and early CK-MB peak. Early coronary reocclusion was detected by early reduction in ST segment elevation followed by stable ST segment re-elevation. Twenty patients (66%) showed successful thrombolytic therapy (Group 1), 5 patients (17%) had no evidence of successful thrombolytic therapy (Group 2) and 5 patients (17%) showed an early reocclusion (Group 3). LF/HF ratio values at T1 were similar in the three groups (5.66 +/- 1.7 vs 5.65 +/- 1.2 vs 5.51 +/- 0.9, NS). At T2, LF/HF ratio was significantly higher in Group 1 and 3 than Group 2 patients (9.21 +/- 1.7 and 11.1 +/- 1.2 vs 5.58 +/- 1.4, respectively, p < 0.001). In Group 1 LF/HF ratio was significantly lower at T3 when compared with T1 and T2 (1.9 +/- 1 vs 5.66 +/- 1.7 and 9.21 +/- 1.7, respectively, p < 0.001). Conversely, in Group 3 LF/HF ratio at T3 was similar to values measured at T1 (5.59 +/- 1.7 vs 5.51 +/- 0.9, respectively, NS) and significantly higher than those detected in Group 1. In Group 2, LF/HF ratio resulted substantially unchanged at T3 (5.49 +/- 1.7, NS). In conclusion, 1) successful thrombolytic therapy induces early beneficial effects on the autonomic nervous system function, as shown by increased heart rate variability values, when compared with failed thrombolytic therapy; 2) however, during the early period following coronary reperfusion, a transient but dramatic increase in sympathetic activity is observed. This could trigger coronary flow instability, thus facilitating reocclusion, by activating different pathogenetic mechanisms (increased vascular tone, platelet activation, thrombogenic factor prevalence); 3) early coronary vessel reocclusion precludes favorable effects of reperfusion on sympatho-vagal balance observed after the first 24 hours.

Abstract: Cardiac metastases are uncommon but seem to be increasing in incidence, possibly in relation to prolonged survival of cancer patients. Leiomyosarcoma metastatic to the heart is extremely rare. We report the case of a 57-year-old woman previously treated for uterine leiomyosarcoma who presented with dyspnea, electrocardiographic changes mimicking myocardial infarction, and normal enzymes. A left intraventricular mass, suspected as cardiac metastasis, was revealed by echocardiography. The patient died 1 week later. At autopsy the mass proved to be histologically a metastasis of the uterine tumor.

Abstract: Malignant neuroleptic syndrome (alteration of consciousness, muscle rigidity and hyperthermia) is a potentially lethal condition, due also to its life-threatening complications. In particular, hypokinetic and hyperkinetic arrhythmias can be rare and severe early manifestations of this illness, and they deserve a careful approach because of their drug-refractoriness. Arrhythmias associated with the malignant neuroleptic syndrome depend on various mechanisms: neurotransmitter receptor blockades typical of neuroleptic drugs, clustered lipid droplets among the cardiac myofibrils and possible electrolytic disorder due to diaphoresis. The two cases described here presented hypokinetic and hyperkinetic (supraventricular and ventricular) arrhythmias. The arrhythmias, which failed to respond to antiarrhythmic drugs, were temporarily suppressed by DC shock, over-drive pacing and correction of electrolytic imbalance. In case 1, prolonged bromocriptine treatment was required. Complete wash-out of the causative agents resulted in lasting regression of arrhythmias. In conclusion, a correct treatment and a favourable outcome of this syndrome can be achieved only through early diagnosis.

Abstract: A 48-year-old woman with no cardiovascular risk factors was admitted to the hospital because of acute dyspnea. At 27-year-old, she developed Hodgkin's disease, that was successfully treated with splenectomy, combined chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone-MOPP regimen) and radiotherapy (4500 rads). At 43-year-old the lymphoma relapsed and she had further chemotherapy with doxorubicin, bleomycin, vinblastina and dacarbazine. After this treatment, she had an episode of pulmonary edema, attributed to doxorubicin acute cardiotoxicity. She responded to digitalis and diuretics and was discharged with an electrocardiogram (ECG) showing left bundle branch block and a normal echocardiogram. The patient enjoyed good health for several years and 4 months before the present admission the ECG and echocardiogram were unchanged. On this admission there were signs of left ventricular failure with acute pulmonary edema, and a new soft apical murmur (3-4 Levine). The patient required endotracheal intubation and high doses of diuretics, digitalis and vasodilators. The cardiac enzymes were negative, the serial ECGs confirmed left bundle branch block, while the echocardiogram showed moderate to severe mitral regurgitation, akinesia of the interventricular septum and inferior wall with dilation of the left ventricle. A previous silent myocardial infarction was suspected. After recovery, she underwent cardiac catheterization confirming akinesia of the interventricular septum and inferior wall with moderate mitral regurgitation, while coronary angiography showed a critical ostial stenosis of the right coronary artery. In view of a dipyridamole-thallium scan negative for myocardial viability, reperfusion was not attempted. With changes in radiotherapeutic techniques, the incidence of radiation-induced heart disease (pericarditis, myocarditis, conduction abnormalities and, rarely, occlusive coronary artery disease) is declining. Nevertheless, after irradiation of the chest and mediastinum a longterm cardiological follow-up is useful in selecting patients at higher risk of radiation-induced coronary artery disease, who will eventually require coronary angiography and reperfusion intervention.

Abstract: The authors report a case of an acute aortic dissection in a sixty year old patient who two months previously had an ischemic cerebral vascular accident. On the basis of a remittent fever and of raised acute phase proteins the authors suspected a giant cell arteritis as possible pathogenic cause of the clinical presentation. Ruled out infective and neoplastic disorders, after an unhelpful temporal artery biopsy, steroid treatment was introduced at the recommended dosage. Three months after, while reducing steroid therapy, the acute phase proteins raised again to come back to normal values only after restoring full steroid dosage. This pattern of response to steroid treatment may further support the diagnosis of giant cell arteritis even after an unhelpful temporal artery biopsy.

Abstract: Although the efficacy of intravenous thrombolysis in the treatment of acute myocardial infarction has been widely proved, some uncertainty concerning the "temporal window" of administration still persists. The aim of the present investigation was to study whether the late administration of a thrombolytic agent (6 or more hours after the onset of symptoms of acute myocardial infarction) offers any short or long-term advantages with regards to left ventricular function and clinical outcome. We studied 100 consecutive patients at their first episode of myocardial infarction, admitted to Coronary Unit within 24 hours of the onset of symptoms. Of these patients, 62 were administered rt-PA (44 patients within the 6th hour, and 18 between the 6th and 24th hour after the onset of symptoms) and the 38 remaining patients, who did not receive the thrombolytic agent (due to concerns with respect to possible complications), constituted the control group (18 admitted within 6 hours and 20 between 6 and 24 hours). All patients underwent serial electrocardiograms, and echocardiograms upon admission and at discharge to assess the ejection fraction, the asynergy score and the percentage of ischemic area. Furthermore, the survivors were invited for a follow-up examination one year after their acute initial episode. Seven cases of heart failure occurred, before discharge, among the control patients admitted 6 to 24 hours after onset of symptoms, compared with no cases in the subgroup of patients treated with rt-PA during the same time period (p = 0.0068).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Three patients fulfilling criteria for Sudeck's atrophy (reflex sympathetic dystrophy syndrome--RSDS) are described and etiological, pathogenetic and clinical features of the disease are reviewed. RSDS is associated with a wide variety of precipitating factors, each of whom, often in concomitance with metabolic diseases and psychiatric disturbances, may cause the same clinical syndrome, which continues in a "vicious circle" of feed-back mechanisms, correlated with sympathetic hyperactivity. The symptoms may begin gradually and the disorder progresses in stages lasting from weeks to months. The management has not yet been established. Generally, the earlier the syndrome is recognized, the better the results of treatment will be. Analgesics, salmon calcitonin and physiokinesitherapy are recommended. Psychological support is advisable. In more severe patients sympathetic blockade and surgical sympathectomy may be necessary. The effects of hyperbaric oxygen treatment must still be assessed.

Abstract: The authors report the case of a sixty-seven-year-old man with seronegative rheumatoid arthritis since 1967. After the treatment was discontinued, a symptomatic pericardial effusion developed during an exacerbation of rheumatoid arthritis. Histological findings suggested a rheumatoid origin. Consecutive pericardiocentesis and a concomitant adequate treatment resolved cardiac tamponade, at least during short-term follow-up. However, a long term observation will be necessary to exclude recurrent effusion or evolutive constrictive pericarditis.

Abstract: We report a case of a 73-year old railwayman with an asymptomatic large pericardial effusion diagnosed by a routine echocardiogram. By clinical and laboratory tests we excluded an immune, infectious, tuberculous and neoplastic origin of the pericardial effusion. A computed tomography scan of the thorax showed left pleural plaques. Pleural and pericardial biopsies showed fibrohyaline plaques and diffuse aspecific, chronic inflammation consistent with asbestos exposure. By using steroid treatment there was no further evidence of pericardial inflammation or pericardial effusion at 8 month follow-up. Steroid drugs are therefore suggested as a first choice treatment in patients with pleuropericardial effusion as well as chronic asbestos exposure.