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Introduction: Stroke remains a major cause of death and disability in Japan and worldwide. Detecting individuals at high risk for stroke to apply preventive approaches is recommended. This study aimed to develop a stroke risk prediction model among urban Japanese using cardiovascular risk factors., Methods: We followed 6,641 participants aged 30-79 years with neither a history of stroke nor coronary heart disease. The Cox proportional hazard model estimated the risk of stroke incidence adjusted for potential confounders at the baseline survey. The model's performance was assessed using the receiver operating characteristic curve and the Hosmer-Lemeshow statistics. The internal validity of the risk model was tested using derivation and validation samples. Regression coefficients were used for score calculation., Results: During a median follow-up duration of 17.1 years, 372 participants developed stroke. A risk model including older age, current smoking, increased blood pressure, impaired fasting blood glucose and diabetes, chronic kidney disease, and atrial fibrillation predicted stroke incidence with an area under the curve = 0.76 and p value of the goodness of fit = 0.21. This risk model was shown to be internally valid (p value of the goodness of fit in the validation sample = 0.64). On a risk score from 0 to 26, the incidence of stroke for the categories 0-5, 6-7, 8-9, 10-11, 12-13, 14-15, and 16-26 was 1.1%, 2.1%, 5.4%, 8.2%, 9.0%, 13.5%, and 18.6%, respectively., Conclusion: We developed a new stroke risk model for the urban general population in Japan. Further research to determine the clinical practicality of this model is required., (© 2021 S. Karger AG, Basel.)

Background: Health care quality and insurance coverage have improved with economic development in China, but the burden of cardiovascular diseases (CVDs) continues to increase with ongoing gaps in prevention. We aimed to compare the uptake of secondary CVD prevention between stroke and coronary heart disease (CHD) patients in China., Methods: In a cross-sectional community-based survey of 47,841 adults (age ≥45 years) in 7 regions of China between 2014 and 2016, we identified those with a history of stroke or CHD to quantify disparities in conventional secondary CVD prevention strategies in multivariable logistic regression models., Results: There were 4,105 and 1,022 participants with a history of stroke and CHD, respectively. Compared to participants with CHD, those with a history of stroke were significantly less likely to be taking blood-pressure-lowering (39.7% vs. 53%), lipid-lowering (13.7% vs. 36.8%), and antiplatelet (20.8% vs. 50.6%) agents, at least one (48.9% vs. 70.8%) or all 3 recommended medicines (6.1% vs. 24.0%), and were less likely to achieve a lipid-cholesterol target (30.3% vs. 44.0%). Participants with a history of stroke achieved less optimal secondary prevention goals for medication use, either from any (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.44-0.66) or all 3 medications (aOR 0.27, 95% CI 0.20-0.36), as well as better blood pressure (aOR 0.81, 95% CI 0.66-0.98) and low-density lipoprotein cholesterol (aOR 0.34, 95% CI 0.27-0.43) levels of control. There were no significant differences in weight, smoking, or physical activity between the groups., Conclusion: Stroke patients had lower use of secondary CVD-preventive medication and achieved lower levels of risk factor control than those of CHD patients in China. Nationwide disease-specific strategies, and better education of participants and health care providers, may narrow these gaps., (© 2021 S. Karger AG, Basel.)

Background: Kallistatin and ENOX1 are regulators of inflammation and oxidative stress which are typical pathological reactions in atherosclerosis. However, there is limited information of kallistatin and ENOX1 in coronary heart disease (CHD)., Methods: Fifty healthy controls, 56 stable angina pectoris (SAP) patients, and 47 acute coronary syndrome (ACS) patients were included in this study. Levels of kallistatin and ENOX1 in serum were measured by ELISA. χ2 test was performed to analyze categorical data. ANOVA, Pearson correlation analysis, and multiple linear regression were performed to analyze the numerical data. Finally, receiver operating characteristic (ROC) curve was applied to assess the diagnostic value of kallistatin in CHD., Results: Among the 153 participants, 59.5% were male and the average age was 63.8 ± 11.39 years. Compared with the control group, kallistatin expression was decreased in the SAP and ACS groups while expression of ENOX1 was increased in the ACS group (p < 0.05). Pearson correlation analysis showed that the kallistatin level was negatively correlated with the Gensini score (r = -0.210, p < 0.01), white blood cell (WBC) count (r = -0.283, p < 0.001), and triglyceride levels (r = -0.242, p < 0.01) and positively correlated with age (r = 0.353, p < 0.001) and high-density lipoprotein cholesterol (r = 0.310, p < 0.001). ENOX1 expression was positively correlated with WBC count (r = 0.244, p < 0.01), international normalized ratio (r = 0.177, p < 0.05), and Gensini score (r = 0.201, p < 0.05). Multiple linear regression showed that Cr, alanine transaminase, glucose, and kallistatin are independent predictors for Gensini score. The ROC curve showed that kallistatin had the highest diagnostic significance (p = 0.007) when the area under curve was 0.636, with a sensitivity of 0.735 and a specificity of 0.495., Conclusion: Expression of kallistatin was decreased in CHD patients and that of ENOX1 was increased in ACS patients. Kallistatin and ENOX1 were closely connected with the severity of CHD, and kallistatin may be helpful in the diagnosis of CHD., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Subclinical cancer can manifest as a thromboembolic event and may be detected at a later interval in ischemic stroke survivors. We determined the rate of incident cancer and effect on cardiovascular endpoints in a large cohort of ischemic stroke survivors., Methods: An analysis of 3,680 adults with nondisabling cerebral infarction who were followed for two years within the randomized, double-blinded VISP trial was performed. The primary intervention was best medical/surgical management plus a daily supplementation of vitamin B6, vitamin B12, and folic acid. We calculated age-adjusted rates of incidence of cancer among ischemic stroke survivors and standardized incidence ratios (SIR) with 95% confidence intervals (CI) based on comparison with age-adjusted rates in the general population. The significant variables from univariate analysis were entered in a Cox Proportional Hazards analysis to identify the association between various baseline factors and incident cancer after adjusting age, gender, and race/ethnicity. A logistic regression analysis evaluated the association between incident cancer and various endpoints including stroke, coronary heart disease, myocardial infarction, and death after adjusting age, gender, and race/ethnicity., Results: A total of 3,247 patients (mean age ± SD of 66 ± 11; 2,013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 months, 1 year, and 2 years, respectively. The age-adjusted annual rate of cancer in patients with ischemic stroke was higher than in persons in the general population at 1 year (581.8/100,000 persons vs. 486.5/100,000 persons, SIR 1.2, 95% CI 1.16-1.24) and 2 years (1,301.7/100,000 vs. 911.5/100,000, SIR 1.4, 95% CI 1.2-1.6) after recruitment. There was a higher risk for death (odds ratio (OR) 3.1, 95% CI 1.8-5.4), and composite endpoint of stroke, coronary heart disease, and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident cancer compared with those who were cancer free after adjusting for potential confounders., Conclusions: The annual rate of age-adjusted cancer incidence was higher among ischemic stroke patients compared with those in the general population. The odds of mortality were three folds higher among stroke survivors who developed incident cancer., (© 2015 S. Karger AG, Basel.)

Introduction: Individuals with kidney disease are at increased risk for coronary heart disease (CHD) and CHD is associated with an increased prevalence of chronic kidney disease (CKD). Awareness of CKD may potentially influence diagnostic decisions, life-style changes and pharmacologic interventions targeted at modifiable CHD risk factors. We describe here the degree to which persons with CHD are aware of their CKD., Methods: The Reasons for Geographical and Racial Difference in Stroke (REGARDS) cohort study, a population-based sample of US residents aged 45 and older. We included in our analyses 28,112 REGARDS participants recruited as of June 2007. We estimated GFR (eGFR) using the MDRD equation, defined CKD as a GFR <60 ml/min/1.73 m(2), and ascertained awareness of chronic kidney disease and coronary heart disease through self-report. We used the odds ratio to compare the association between awareness of kidney disease, as measured by GFR <60 ml/min/1.73 m(2), among individuals with and without self-reported CHD by both the presence of CKD and the severity of impaired kidney function., Results: Coronary heart disease was reported by 3,803 (14.1%) of subjects, and 11.3% of subjects had CKD by eGFR. Among all individuals with a GFR <60 ml/min/ 1.73 m(2), 9.6% reported having been told by a physician that they had kidney disease. Among those with CHD and CKD, 5.0% were aware of their CKD compared to 2.0% in those without CHD [OR (95% CI) = 2.57 (2.08, 3.28)]. This difference persisted after controlling for the level of kidney function [aOR (95% CI) = 1.87 (1.43, 2.41)]., Conclusion: There was a high prevalence of CKD and a low prevalence of awareness of kidney disease among older adults in the US population with or without coronary heart disease. These findings support recent recommendations that patients with cardiovascular disease be systematically screened for and educated about CKD., (Copyright 2008 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF) is a common arrhythmia encountered following cardiac surgery. Previously, we have shown that higher expression of heat shock protein (HSP) 70 was associated with decreased incidence of postoperative AF (PoAF), suggestive of an antiarrhythmic role., Objective: We have hypothesised that Met493Thr substitution of one of the important hsp70 genes may cause loss of these protective antiarrhythmic effects. We therefore set out to examine the influence of hsp70 genotype on the incidence of PoAF., Methods and Results: We prospectively recruited 244 Caucasian patients undergoing elective coronary artery bypass surgery. The median age was 65 years (40-80 years). PoAF was defined as the characteristic arrhythmia lasting for at least 15 min, occurring within first week following surgery and requiring treatment. This occurred in 48 patients (19.7%). Validated Met493Thr substitution in hsp70-Hom was determined using established techniques. Of 244 patients, genotype was determined for 242 cases. The three genotypes (MM, MT, and TT) were present at frequencies of 0.66, 0.31, and 0.03, respectively, and were in Hardy-Weinberg equilibrium. In unifactorial analysis patients carrier or homozygous for 493Thr mutation had significantly higher incidence of PoAF (Pearson chi(2) = 4.3, p = 0.037). Multivariate analysis confirmed the positive association of hsp70-Hom with PoAF (OR, 2.43; p = 0.016) independent of age, sex, previous myocardial infarction, number of distal anastomoses, and duration of ventilation, respectively. Serum HSP70 was ranging from 0.74 to 31.91 ng/ml (median, 2.89) and was not correlated with PoAF. Presence of 493Thr mutation was also significantly correlated with higher levels of serum HSP70 (p = 0.009)., Conclusions: Our data show that a mutation in hsp70-Hom gene is associated with higher incidence of PoAF. These findings are consistent with our previous results and may suggest that patients harbouring this substitution will have less endogenous myocardial protection against AF in stressful situations.

Aims: The aim was to assess the association between panic disorder (PD) and the long-term outcome of chest pain patients with or without coronary artery disease (CAD)., Methods: Patients (n = 199) consecutively referred to a cardiology outpatient clinic because of chest pain were reassessed after 9 years. At the initial examination 16% suffered from CAD and 38% from PD. Data were collected on mortality, cardiac events, cardiac risk factors, chest pain, anxiety and depression (SCL-90-R), and health-related quality of life (SF-36)., Results: The death rate in the study population was not significantly different from that in the general population and no significant associations were found between PD at baseline and mortality and cardiac morbidity at follow-up. PD was associated with significantly higher follow-up scores of chest pain intensity (p = 0.025), depression (p = 0.005), anxiety (p = 0.039), and poorer health-related quality of life: physical functioning (p = 0.004), role physical (p = 0.001), body pain (p = 0.007), and general health (p < 0.001)., Conclusions: PD has a negative long-term effect on psychological and physical well-being of chest pain patients which emphasizes the necessity of identifying PD patients and offering them adequate treatment.

Background: Causes of ischemic stroke in young adults (15-45 years) are diverse, but undetermined etiology is common in a majority of studies., Aims: The present series study aims to evaluate causes and changes in the etiological diagnosis of ischemic stroke in young adult patients admitted to a tertiary medical center over a period of 27 years., Methods: We retrospectively reviewed the records of patients with a first-ever stroke in the age range of 15-45 years who were admitted to the '12 de Octubre' University Hospital between 1974 and 2002., Results: 272 young adults with ischemic stroke were identified. The etiological diagnoses were: undetermined in 36% of patients, large-artery atherosclerosis in 21%, cardioembolism in 17%, non-atherosclerotic vasculopathy in 17%, and other specific etiologies in 9%. While in the first study period (1974-1988) 45% of patients were diagnosed with uncertain etiology, in the last period (1989-2002) only 26% were diagnosed with cryptogenic stroke (45% with two or more potential etiologies identified; 45% with no identified cause despite complete evaluation, and 10% with incomplete evaluation)., Conclusions: The etiological diagnosis of stroke in young adults has changed over time as a result of improvements in diagnostic workup. While cryptogenic stroke was the most frequent diagnosis in the past, today specific causes (non-atherosclerotic vasculopathy, large-artery atherosclerosis, cardioembolism and hematological disorder) are identified in the majority of patients., (2007 S. Karger AG, Basel)

Background: Coronary heart disease (CHD) is very common among elderly people., Objective: To specify the diagnostic value of bicycle exercise tests conducted for elderly patients by trained general practitioners in primary health care., Methods: We performed a 2-year follow-up study at the Kangasala Health Centre, Finland. The study population comprised all patients at least 60 years old (n = 311) suspected of having CHD without prior diagnosis who were examined by an exercise test carried out by trained general practitioners during a period of 3 years. Specificity and sensitivity as well as positive and negative predictive values of the tests were calculated based on whether or not the participants had a diagnosis of CHD by the end of the follow-up period. The numbers of patients referred for coronary angiography and bypass operation were registered. For analysis, the patients were divided into two age categories: 60-69 years and >or=70 years., Results: A negative finding in the test proved very reliable: CHD manifested in only 3% of these cases in both age groups. The specificity of the test was 72% in the group 60-69 years and 66% in the group >or=70 years; the sensitivity values were 81 and 67%, respectively. The positive predictive values were 26 and 12%, the negative predictive value was 97% in both age groups. 1 in 4 patients yielding a positive finding eventually underwent coronary angiography and 1 in 6 patients coronary bypass surgery., Conclusions: Exercise tests may predict the clinical outcome of CHD among elderly patients. A negative finding in an exercise test is very reliable., (Copyright 2007 S. Karger AG, Basel.)

Published guidelines recommend continuing beta-adrenergic receptor blockade in patients undergoing stress testing. We evaluated the role of pharmacological versus exercise stress testing in achieving target heart rate (THR) among patients on beta-adrenergic blockade. We compared data from 140 patients who underwent dobutamine stress echo (DSE) and 143 patients who underwent exercise treadmill testing (ETT). In both groups, beta-adrenergic blocker was continued at the time of stress testing. Overall, patients undergoing DSE achieved THR more frequently than ETT. With beta-adrenergic blockade, DSE patients met THR more frequently than ETT patients (p < 0.001). Without beta-adrenergic blockade, there was no difference between either modality in achieving THR. In both DSE and ETT patients, absence of beta-adrenergic blockade increased the odds of achieving THR [odds ratio (OR): 2.46, p = 0.042 and OR: 7.44, p < 0.001, respectively]. Atropine use with DSE increased the odds of achieving THR (OR: 3.76, p = 0.006). In conclusion, pharmacological stress testing appears to be superior to exercise stress testing in achieving THR among patients on beta-adrenergic blockade., (Copyright 2005 S. Karger AG, Basel.)

Introduction: Cardiac troponin T (cTnT) is often elevated in hemodialysis (HD) patients without acute coronary syndrome (ACS). The aim was to assess the predictive value for mortality of pre-dialysis cTnT in asymptomatic patients. If patients became symptomatic during follow-up, cTnT was followed to assess its diagnostic value for ACS., Methods: Forty-nine asymptomatic HD patients were included: 30 patients with a history of cardiovascular disease (CV+) and 19 without (CV-). In 11 patients cTnT, myoglobin and creatine kinase (CK) were measured before and during HD. During ACS, cTnT was followed until recovery. A cTnT of > or =0.03 mug/l was considered elevated. Follow-up was 2 years., Results: cTnT was elevated in 82% (40/49). More CV+ patients had an elevated cTnT (28/30) than CV- patients (12/19; p = 0.02). There was no change in cTnT, myoglobin and CK during HD. During ACS, cTnT increased above baseline, and tended to return to baseline after recovery. Mortality was 33% (16/49). Patients with elevated cTnT had a higher mortality rate (16/40) than patients with negative cTnT (0/9; p = 0.02)., Conclusions: Elevated cTnT levels in asymptomatic HD patients are not caused by acute myocardial injury or by HD itself. They may be related to chronic myocardial damage and decreased clearance, and are of prognostic value. During ACS, however, a cTnT rise above the individual baseline is diagnostic of acute myocardial injury., (Copyright (c) 2004 S. Karger AG, Basel.)

Background: The prevalence of the metabolic syndrome (MS) is growing. The Adult Treatment Panel (ATP) III provided a uniform definition of MS but no information on its predictive ability., Methods: We tested the ability of MS and its components to predict angiographic coronary artery disease (CAD) and incident death/myocardial infarction (D/MI) over 2.8 +/- 2.3 years in a large cohort of patients undergoing angiography. ATP-III criteria were used for fasting glucose (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and blood pressure (BP); body mass index (BMI) >27 kg/m(2) was used as a surrogate for waist circumference., Results: 3,128 subjects were studied; 65% had advanced CAD (>/=70% stenosis), and 35%, no CAD. MS was present in 64% (high FG 40%; high TG 52%; low HDL 71%; high BP 76%; high BMI 58%). Presence of CAD was predicted by MS [adjusted odds ratio (OR) = 1.30, 95% CI 1.10-1.55, p = 0.003] and, individually, by high FG (OR = 1.90, CI 1.63-2.23) and low HDL (OR = 1.38, CI 1.18-1.62). In multivariable modeling, CAD was predicted by high FG (OR = 1.80, CI 1.51-2.16) and low HDL (OR = 1.57, CI 1.31-1.89) as well as by age, gender, family history, smoking, and LDL cholesterol (all p < 0.001). For secondary risk of incident D/MI, only high FG of MS features was predictive (adjusted hazard ratio 1.46, CI 1.17-1.82, p = 0.001), and this risk was carried by diabetes (adjusted hazard ratio 1.71, p < 0.001); other predictors were age, heart failure, revascularization strategy, renal insufficiency, prior MI, and number of diseased vessels., Conclusion: MS has primary predictive ability for CAD, carried primarily by high FG and low HDL. Secondary predictive ability of MS features for clinical outcomes, in the setting of established CAD, is carried by diabetes alone. Dysglycemia deserves specific attention as a target for prevention and treatment., (Copyright 2004 S. Karger AG, Basel)

We evaluated the clinical outcome and the prognostic factors at 6-year follow-up of patients with acute coronary syndrome without critical coronary arterial narrowing. The mean follow-up was 73 +/- 19 months. Mortality rate was 13%, and 20 patients (12%) had major cardiac event, 8 patients (5%) had stroke and 10 patients (6%) underwent revascularization. Multivariate analysis matched for age and ejection factor showed that moderate disease (stenosis 40-59%) (OR = 2.713, p < 0.024) was an independent predictive factor of major cardiac event., (Copyright 2003 S. Karger AG, Basel)

This randomized, single-blind, placebo-controlled study investigated the effect of ivabradine, a novel heart rate-lowering agent, on echocardiographic indices of left ventricular (LV) systolic function in patients with regional (coronary artery disease) or global (cardiomyopathy) LV dysfunction. Patients were randomized on an unequal basis to receive ivabradine 0.25 mg/kg (n = 31) or placebo (n = 13) by intravenous infusion. Resting heart rate was reduced by a mean of 17.6 +/- 4.7% with ivabradine and 1.5 +/- 5.8% with placebo. The mean maximum decrease in LV ejection fraction was 0.2% with ivabradine and 1.7% with placebo. Fractional shortening and stroke volume were also fully preserved after ivabradine administration. Thus, a single intravenous dose of ivabradine produced a substantial reduction in resting heart rate without affecting LV function in patients with regional or global LV dysfunction.

Objective: To report the case of an 85-year-old man with asymptomatic massive hypertriglyceridemia (MHTG)., Clinical Presentation and Intervention: Our case was a non-smoker, healthy 85-year-old Caucasian male, with no excessive alcohol intake and no evidence of an excessive sedentary lifestyle, body mass index = 23.2 kg/m(2), BP = 125/85 mm Hg and plasma triglyceride (TG) >1,000 mg/dl. The MHTG was an incidental finding at the age of 70. He had no cardiovascular disease, xanthomas, xanthelasmas or keratic precipitate. During the last 15 years, his average TG plasma levels showed a significant variability independent of specific diet treatment and fibrate therapy. Liver ultrasound examination excluded hepatomegaly and fatty degeneration. Carotid artery ultrasound showed only intimal thickening in both carotid bifurcations., Conclusion: In this patient, MHTG had been silent for many years, with no evidence of coronary heart disease and liver fatty degeneration, both typical complications present in MHTG subjects with low high-density lipoprotein. Hence, this case must be considered as a rarity., (Copyright 2003 S. Karger AG, Basel)

Background: The syndrome of chest pain associated with characteristic anterior electrocardiographic changes, moderate increases in cardiac enzymes, and a reversible apical wall motion abnormality in the absence of coronary artery disease has been documented in Japan, but has received relatively little attention in other countries., Methods: The clinical and echocardiographic data of 12 patients (11 women, mean age 64 +/-14 years) who presented with chest symptoms, electrocardiographic (ECG) changes indicative of an acute anteroapical myocardial infarction, abnormal cardiac enzyme levels and echocardiography showing an apical wall motion abnormality were collected. Coronary angiography was performed in 10 patients. A follow-up echocardiogram was obtained within 2 weeks of the initial diagnosis in most cases., Results: An identifiable, precipitating ("trigger") event could be identified in all 12 individuals. Respiratory distress was present in 7, the death of a relative in 3, in 4 a surgical or medical procedure had been performed, and in 1 a panic disorder was diagnosed. The echocardiograms showed a characteristic wall motion pattern of significant apical dysfunction. All of the patients who underwent coronary arteriography had noncritical coronary artery disease. Follow-up echocardiography showed normalization of the LV dysfunction in all instances., Conclusion: We identified a syndrome of chest pain, dyspnea, ECG and enzyme changes mimicking acute myocardial infarction, similar to the "Takotsubo" syndrome described in Japan. It is likely that the widespread use of echocardiography, coupled with increased recognition of this syndrome, will result in this diagnosis being made more commonly., (Copyright 2003 S. Karger AG, Basel)

Although heart-type fatty acid-binding protein (H-FABP) can be a marker of sarcolemmal injury due to acute myocardial ischemia, the diagnostic or prognostic value is not established in patients with acute chest pain. This multicenter prospective study aimed to determine the diagnostic and prognostic values of H-FABP in 133 patients presenting to an emergency room with suspected acute coronary syndrome (ACS) by comparing with those of conventional biomarkers. H-FABP and myoglobin had greater positive results than did creatine kinase-MB or troponin T. Receiver operating characteristics analysis revealed that H-FABP was the most reliable for detection of ACS and that H-FABP had the greatest sensitivities for identification of patients requiring emergency hospitalization, coronary angiography, and interventional therapy within 7 days among the biomarkers. Thus, H-FABP can be an early diagnostic and prognostic biochemical marker, particularly within the first 6 h from the onset of chest symptoms, in patients with chest pain at an emergency department., (Copyright 2003 S. Karger AG, Basel)

Background: Disturbance of the hemostatic and the inflammatory system plays an important role in the pathophysiology of acute coronary syndromes (ACS). Their markers have been shown to predict further coronary events in patients with ACS. The prognostic value of the admission electrocardiogram (ECG), which is commonly used to evaluate ischemia, was studied previously. We investigated the correlation between serum markers of the hemostatic/inflammatory system and ECG changes in ACS., Methods: A standard 12-lead ECG was obtained from 85 patients with ACS on admission (0d). Markers of the hemostatic and inflammatory system were measured on admission and after 2 days (2d)., Results: Patients with ST-T-changes had higher fibrinogen and thrombin-antithrombin III complex (TAT) levels than patients without ECG alterations at both times (fibrinogen: 0d: 492 +/- 38 vs. 357 +/- 36 mg/dl, p < 0.01; 2d: 633 +/- 55 vs. 440 +/- 50 mg/dl, p < 0.02; TAT: 0d: 7.2 +/- 1.3 vs. 3.6 +/- 0.7 microg/l, p < 0.05; 2d: 5.3 +/- 0.9 vs. 3.2 +/- 0.5 microg/l, p < 0.05). Tissue-type plasminogen activator (TPA) was elevated in patients with ECG changes initially (10.1 +/- 0.6 vs. 7.2 +/- 0.7 ng/ml, p < 0.02). D-dimers, the acute-phase proteins C-reactive protein, serum amyloid A and the soluble adhesion molecules showed no significance., Conclusions: The data reveal a correlation between electrocardiographic changes and hemostasis in patients with ACS. The association of myocardial damage and a disturbed hemostatic system might stratify patients who are at high risk of suffering further coronary events., (Copyright 2002 S. Karger AG, Basel)

Background: We prospectively examined the relationship between latent constructs of perceived difficult temperament and hostile maternal child-rearing attitudes on the one hand, and the cluster of multiple cardiovascular risk factors comprising the insulin resistance syndrome (IRS) on the other., Methods: A 3-year follow-up study of 451 randomly selected healthy children was used. The temperament of the children and maternal child-rearing attitudes were self-rated by the mothers. The physiological parameters measured were serum insulin, high-density lipoprotein cholesterol (HDL-C), triglycerides, systolic blood pressure, body-mass index and subscapular skinfold thickness. We analyzed the data using structural equation models that involved specific paths allowing separation, and tests of both unique and common (latent) aspects of measured variables., Results: Among boys we found a cross-lagged effect between the latent constructs of perceived difficult temperament and IRS, as well as 1 specific effect from hostile maternal child-rearing attitudes to HDL-C. Among girls there were 6 specific effects from specific measures of perceived temperamental difficultness or hostile maternal child-rearing attitudes that influenced the IRS or its components., Conclusions: The findings suggest that temperament and maternal child-rearing attitudes may contribute to the early development of the IRS in a gender-specific way among children, thereby potentially increasing the risk of coronary heart disease later in life., (Copyright 2001 S. Karger AG, Basel)

Aim: To determine whether the use of inhaled beta-agonists decreases the duration of dobutamine stress testing (DAS), reduces the amount of dobutamine infused and decreases the use of atropine., Methods: 34 patients on beta-agonists (group A) (mean age 65 +/- 8 years) and 32 patients not on beta-agonists or beta-blockers (group B) (mean age 65 +/- 10 years) undergoing DAS with SPECT were enrolled., Results: The time of infusion of dobutamine in group A was 6.41 +/- 1.58 min and in group B was 9.77 +/- 3.60 min (p < 0.001). The amount of dobutamine infused was 10.64 +/- 5 mg in group A and 19.20 +/- 8 mg in group B (p < 0.001). In group A, 2 of 34 patients and 18 of 32 patients in group B needed atropine to reach peak HR (p < 0.001)., Conclusion: Patients on short acting beta-agonists require smaller amounts of dobutamine with a shorter infusion time during DAS, and lesser use of side-effect prone atropine., (Copyright 2001 S. Karger AG, Basel)

Decreased heart rate variability (HRV) is associated with a worse prognosis in a variety of diseases and disorders. We evaluated the determinants of short-period HRV in a random sample of 149 middle-aged men and 137 women from the general population. Spectral analysis was used to compute low-frequency (LF), high-frequency (HF) and total-frequency power. HRV showed a strong inverse association with age and heart rate in both sexes with a more pronounced effect of heart rate on HRV in women. Age and heart rate-adjusted LF was significantly higher in men and HF higher in women. Significant negative correlations of BMI, triglycerides, insulin and positive correlations of HDL cholesterol with LF and total power occurred only in men. In multivariate analyses, heart rate and age persisted as prominent independent predictors of HRV. In addition, BMI was strongly negatively associated with LF in men but not in women. We conclude that the more pronounced vagal influence in cardiac regulation in middle-aged women and the gender-different influence of heart rate and metabolic factors on HRV may help to explain the lower susceptibility of women for cardiac arrhythmias., (Copyright 2001 S. Karger AG, Basel)

Calcium antagonists have long been used as first-line drugs for hypertension and angina. However, deleterious effects have also been reported in patients treated with calcium antagonists. Thus, we evaluated the effect of a slow-release twice-daily formulation of nifedipine in 10 patients with severe coronary artery disease. Twenty-four-hour ambulatory electrocardiography (AECG) and blood pressure monitoring (ABPM) were performed simultaneously to detect any association between ischemic episodes on the ECG and changes in blood pressure (BP) and heart rate with and without nifedipine. Increased oxygen demand due to an increased systolic BP and heart rate was associated with ischemic episodes without nifedipine, while those with nifedipine were accompanied by a fall in diastolic BP and a rapid increase in heart rate. This slow-release twice-daily formulation of nifedipine may induce myocardial ischemia through a heart-rate increase and a decrease in coronary blood flow due to lower diastolic BP in patients with severe coronary artery disease. A once-daily formulation of nifedipine might be of great value for such patients., (Copyright 2000 S. Karger AG, Basel.)

Fuzzy cluster analysis (FCA) was used to classify 166 outpatient positive treadmill stress tests as mildly, moderately, or severely abnormal. The method combines ST-segment change with five other stress test variables, and then computes a similarity measure to determine how closely each patient's stress test resembles a prototypical mildly, moderately, or severely abnormal stress test. All patients had coronary angiography within 1 month of their stress tests. For the 45 patients with triple vessel disease (TVD), FCA classified 34 of these stress tests as severely abnormal (sensitivity = 75%). For the 22 patients with left main disease (LM), FCA classified 19 stress tests as severely abnormal (sensitivity = 86%). For the combined group with high-grade disease (TVD + LM), the sensitivity was 79%. A literature review shows that for stress echocardiography, multiple exercise-induced wall motion abnormalities have a sensitivity in the 70-80% range for patients with high-grade disease. For nuclear stress testing, the high-risk pattern of multiple reversible defects, with or without increased lung uptake, has a sensitivity in the range of 70-80% for patients with high-grade disease. Thus classification of a positive stress test as severely abnormal by FCA has a sensitivity comparable to high-risk patterns on stress echocardiography and nuclear stress testing in patients with TVD or LM.

Although the mechanism underlying coronary conduit artery spasm in vasospastic angina (VAP) remains unknown, coronary endothelial dysfunction has been suggested as playing an important role. However, it remains unknown whether this endothelium-mediated abnormal vasomotion is uniformly evident irrespective of site of vascular bed or vessel size. Plethysmographic studies were carried out to measure changes in forearm resistance vessel blood flow (FBF) induced by acetylcholine (Ach), sodium nitroprusside, and 10-min occlusion-induced reactive hyperemia in 12 patients with VAP, 14 patients with atherosclerotic (>75% fixed stenosis) coronary artery disease (CAD), and 16 healthy controls. FBF responses induced by the endothelium-dependent vasodilator Ach were significantly augmented in patients with VAP compared to controls, whereas this type of FBF response in patients with CAD was significantly blunted (at the maximum dose: VAP, 24.1 +/- 3.0; controls, 17.2 +/- 1.9; CAD, 12.8 +/- 1.9 ml/min per 100 ml; p < 0.01). However, there were no significant differences in FBF responses during infusion of sodium nitroprusside among the three subject groups. Reactive hyperemic FBF which represents maximum vasodilatory capacity did not differ among the three. To assess the role of nitric oxide in the augmented endothelium-dependent response in VAP, Ach-induced FBF response was determined before and after administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine in another VAP group (n = 7). After nitric oxide synthase inhibition, the peak FBF response induced by Ach decreased from 23.3 +/- 3.2 to 14.1 +/- 1.6 ml/min per 100 ml (p < 0.05). In conclusion, the above data suggest that endothelium-dependent vasomotor response to Ach in limb resistance vessels is augmented in patients with vasospastic angina. It seems unlikely that endothelial function is consistently depressed in any area of the vascular bed in this disorder., (Copyright 2000 S. Karger AG, Basel)

A slowly upsloping ST segment depression is an abnormal, and a rapidly upsloping ST segment depression is a normal exercise ECG response. We investigated the agreement of expert physicians on the visual classification of the ST segment depression, and compared the (majority) vote with the computer-generated ST slope. A total of 206 exercise ECG leads with an amplitude of the ST segment depression > or = 0.15 mV and a ST segment slope > or = 0.5 mVs(-1) were evaluated. All three interpreters agreed in 68 cases, two agreed in 123 cases, and all disagreed in 15 cases. Intraobserver agreement was 61%. The ST segment slope was significantly (p < 0.001) greater in leads generally interpreted as rapidly upsloping (n = 38; 2.1 +/- 0.8 mVs(-1)), than in those interpreted as slowly upsloping (n 121; 1.3 +/- 0.6 mVs(-1)) or horizontal (n = 32; 1.1 +/- 0.4 mVs(-1)), although there was some overlap. Thus, standardization of the computer-assisted exercise ECG interpretation should be continued.

To determine whether increased intracellular levels of magnesium ([Mg]i) are associated with enhanced functional capacity, we performed symptom-limited exercise treadmill testing on 42 stable coronary artery disease (CAD) patients (37 men, 5 women, mean age 68 +/- 9 years). [Mg]i was found to be an independent and significant predictor of exercise duration (R = 0.31, p = 0.02) in a multivariate stepwise regression model. Patients with > normal [Mg]i of 1.23 microg/mg protein (n = 13) had a significantly greater mean functional capacity, measured in higher achieved metabolic equivalents (10.6 +/- 2.5 vs. 8.9 +/- 2.3, p < 0.05) and exercise duration (9.4 +/- 2.3 vs. 7.9 +/- 2.2 min, p < 0.05) compared to patients with [Mg]i

Background/aims: This study examined the role of diabetes mellitus on determining left ventricular function by evaluating coronary artery diameter in patients with end-stage renal disease on maintenance hemodialysis treatment., Methods: We studied 12 diabetic and 12 nondiabetic patients on maintenance hemodialysis treatment without significant stenoses of the major epicardial coronary arteries. Patients were matched for age, sex distribution, duration of dialysis and incidence of major coronary risk factors. Left ventricular wall thickness (septal and posterior walls) and left ventricular diameter (end-diastolic and systolic phases), were measured by echocardiography. Hemodynamic measurements and coronary angiography were performed on the day of hemodialysis and coronary artery diameter at the proximal and mid portion of three major coronary arteries were measured using the computed densitometry method., Results: Right and left anterior descending and circumflex coronary artery diameters were all significantly smaller and the frequency of coronary artery calcification was higher in diabetic (58%) compared to nondiabetic (8%) patients. Although there were no significant differences in left ventricular wall thickness, left ventricular diameter, mean right atrial pressure and cardiac index between the two groups, left ventricular end-diastolic pressure was significantly higher in diabetic (22 +/- 9 mm Hg) compared to nondiabetic patients (14 +/- 5 mm Hg)., Conclusion: Despite that there were no significant stenoses of the major epicardial coronary arteries, diffuse luminal narrowing of the epicardial coronary arteries in diabetic patients on maintenance hemodialysis treatment was associated with increased left ventricular end-diastolic pressure.

In this prospective study, we examined the diagnostic accuracy of exercise-induced left QRS axis deviation as a marker of LAD coronary artery stenosis. The mean frontal QRS axis of 66 consecutive patients with chest pain and exercise-induced ST segment depression referred for diagnostic coronary angiography was analyzed and related to the angiographic findings. An exercise-induced leftward QRS axis deviation was found in 9/40 patients with and 0/26 patients without obstructive (> or = 70%) LAD disease (sensitivity 23%, specificity 100%, p = 0.025). In 7 of the 9 patients with left axis deviation, the lesion was proximal to and in 2 in the region of the first septal perforator. Inclusion of patients with 0 degrees exercise-induced QRS axis deviation provided a more sensitive but less specific marker of LAD disease [sensitivity 53% (21/40), specificity 81% (21/26), p = 0.015]. The findings were similar in patients with single and with multivessel coronary artery disease. Grouping all patients in the present prospective and two previous retrospective studies (n = 165), the sensitivity was 29% and specificity 100% (p < 0.0001). Exercise-induced left QRS axis deviation was a highly specific marker of LAD coronary artery stenosis.

The S-T segment/heart rate (ST/HR) slope has been proposed as a more accurate electrocardiographic criterion for the diagnosis of coronary artery disease, but studies comparing the diagnostic value of the ST/HR slope with exercise thallium imaging are scant. The aims of this study were to assess the diagnostic accuracy of the ST/HR slope, conventional S-T segment criteria and exercise thallium imaging in detecting coronary artery disease and to evaluate the effect of exercise level on the sensitivity and specificity of these three techniques. Ninety consecutive patients underwent treadmill testing and exercise thallium single-photon emission computed tomography (SPECT) simultaneously. All 90 patients also underwent coronary angiography within 1 month of the exercise test. We found that exercise thallium SPECT had a significantly higher diagnostic accuracy than either the ST/HT slope or conventional S-T segment criteria (thallium imaging 82%, ST/HR slope 67%, conventional S-T segment criteria 63%). The overall accuracy of the ST/HR slope was slightly but insignificantly greater than conventional S-T segment criteria (ST/HR slope 67%, conventional S-T segment criteria 63%; p = 0.639). In 50 patients with a lower exercise level, defined as not achieving 85% of their maximal predicted heart rate, the accuracy of the ST/HR slope was insignificantly greater (ST/HR slope 72%, conventional S-T segment criteria 66%; p = 0.517). In 40 patients with adequate exercise, the accuracy rate was the same (60%) for both the ST/HR slope and conventional S-T segment criteria. We conclude that exercise thallium imaging is more accurate than the ST/HR slope in diagnosing coronary artery disease and that the accuracy of the ST/HR slope is marginally better than conventional S-T segment criteria only in patients with a lower exercise level, and not in those with adequate exercise.

Background: Recent studies have suggested that positive troponin I tests are associated with an increased risk of cardiac death during short-term follow-up. However, it is unknown if troponin I tests alone or in addition to CK-MB measurements are superior to predict unfavorable outcome during long-term follow-up., Patients and Methods: In a prospective, double-blind study we assessed the prevalence and prognostic value of combined troponin I and CK-MB tests in an unselected cohort of patients (n = 292) admitted to the emergency department for acute chest discomfort. Patients were grouped according to the diagnosis on discharge in those with acute myocardial infarction (1), unstable angina (2), and noncardiac chest pain (3). Six months after enrollment, death rates were obtained and follow-up interviews were performed with respect to survival, recurrence of chest pain, and myocardial infarction., Results: In patients with evidence of coronary heart disease, the mortality rate for abnormal troponin I and normal CK-MB levels was 5.0%. Baseline troponin I and elevated CK-MB levels were associated with a mortality rate of 4.0%. However, the mortality rate was significantly higher (11.1%) in patients presenting with elevated troponin I and CK-MB values. In patients without myocardial infarction on admission, 10.5% with positive troponin I tests died compared to 1.6% with negative tests. The mortality rate in patients without myocardial infarction was 2.7% for patients with elevated CK-MB but normal troponin I values. In patients with both markers elevated a significantly higher mortality rate (16.7%) was found, representing a 6-fold increase in the death event rate. With the additional knowledge of troponin I values, it could be demonstrated that certain cases were misclassified as having noncardiac chest pain. At least some of the latter patients with above-normal values of troponin I were retrospectively to be reclassified as unstable angina. Acute non-Q-wave myocardial infarctions were occasionally misdiagnosed as either angina pectoris or nonischemic chest pain., Conclusions: Our data suggest the superiority of combined CK-MB and troponin I measurements in clinical practice for the early risk stratification of patients presenting with acute chest pain. In nonmyocardial infarctions, both CK-MB and troponin I convey independent prognostic information with regard to fatal outcome. Troponin I tests in addition to CK-MB measurements contribute to a lower rate of misdiagnoses.

Background: This analysis explores whether 'typical' clinical manifestations of coronary heart disease (CHD) such as myocardial infarction and sudden death, relate to major cardiovascular risk factors in the same way as the 'atypical' manifestations, e.g. heart failure and chronic arrhythmias., Patients and Methods: Sixteen cohorts of men aged 40-59 in seven countries were examined, risk factors measured (age, systolic blood pressure, serum cholesterol and smoking habits) and 25-year mortality data collected in a systematic way. Cohorts were located in the US (n = 1), Finland (n = 2), the Netherlands (n = 1), Italy (n = 3), former Yugoslavia (n = 5), Greece (n = 2) and Japan (n = 2), with a total of 12,763 individuals. Ecological analysis based on regression equations and correlation among cohorts, and individual analyses based on proportional hazard models in pools of cohorts were conducted with typical and atypical CHD deaths as dependent variables., Results: The ecological analysis suggests a significant relationship of populational mean levels of serum cholesterol and of systolic blood pressure to age-adjusted death rates from typical CHD manifestations. The relationships for atypical CHD deaths were not statistically significant. In the ecological approach with multivariate analysis, none of the risk factors showed relevant associations with event rates, except serum cholesterol and typical CHD deaths. The ecological relationship of serum cholesterol to atypical CHD death rates was negative but not significant. On average, mean age at death was statistically higher among atypical CHD than typical CHD patients (70.2 vs. 65.8 years). In the individual multivariate analysis conducted on pools of countries, the relationship of risk factors with typical CHD deaths was direct and significant for age, systolic blood pressure, and smoking habits in Northern Europe and America and Southern Europe, but only for systolic blood pressure and smoking habits in Japan, whereas for atypical CHD, the predictive factors were age, systolic blood pressure and cigarette smoking in Northern Europe and America and Southern Europe, but only age in Japan., Conclusions: The usual relationship of blood pressure and smoking habits and the differential relationship of serum cholesterol with atypical CHD (negative or absent) versus typical CHD (direct and significant) could be explained by 'two different diseases' or by a mix of poorly classified conditions among the atypical cases.

To compare the diagnostic value of dobutamine stress echocardiography with dobutamine thallium-201 single-photon-emission computed tomography (SPECT) in detecting coronary artery disease, we performed both tests simultaneously on 93 patients who also underwent coronary arteriography. Dobutamine was infused at rates of 5, 10, 20, 30 and 40 microns/kg/min in 3-min stages. The left ventricle was divided into anteroseptal, posterolateral and inferior regions. Within each region, wall motion or perfusion abnormalities were classified as normal, ischemia or fixed defect. The response to stress was concordantly classified by both tests in 67 patients (72%, kappa = 0.48). Regional agreement for abnormalities was observed in 79% (kappa = 0.56) of the 279 regions analyzed. Dobutamine echocardiography detected 62 (93%) and thallium SPECT 60 (90%, p = NS) of the 67 patients with significant coronary artery disease (> or = 50% diameter stenosis). The specificity was 77 (20 of 26) and 81% (21 of 26), respectively. The accuracy was 88 and 87%, respectively. Combined the two tests gave a sensitivity of 97%, a specificity of 65% and an accuracy of 88%. The accuracy for detecting individual coronary stenosis with echocardiography was 83% for the left anterior descending artery, 84% for the right coronary artery and 73% for the left circumflex artery. With SPECT, it was 83, 87 and and 76%, respectively. In conclusion, dobutamine stress echocardiography and thallium SPECT provide a comparable accuracy for detection and localization of coronary artery disease, and for identification of regional myocardial abnormalities. Performing the two tests simultaneous is feasible but it adds limited value in detecting coronary artery disease.

We evaluated the functional significance of angiographically successful percutaneous transluminal coronary angioplasty (PTCA) in 50 patients before and after PTCA using an atrial pacing stress test. Before balloon angioplasty, 40/50 patients had transient ST-segment changes on the intracoronary (IC) ECG. After PTCA 14/50 patients continued to have ischemic changes on IC-ECG. Atrial pacing stress tests can be performed easily in the cardiac catheterization laboratory. Despite angiographically successful dilatation, 28% of the patients have inducible ischemia indicating functionally inadequate dilatation. Inadequate functional dilatation may contribute to early return of symptoms in some patients.

Despite an exercise electrocardiogram (ECG) positive for ischemia by established criteria, many patients referred for coronary angiography to evaluate chest pain are found to have angiographically normal coronary arteries (NCA). Exercise ECG were analyzed from 27 patients with chest pain and angiographically NCA and 28 patients with chest pain and coronary artery disease (CAD) using univariate and multivariate logistic regression analysis. We derived the following logistic model for the logit probability of CAD: 3 + SEX x 4 - METs x 0.7 + STDV5 x 0.8, where SEX = 0 for female and SEX = 1 for male, METs = maximal estimated work load (metabolic equivalents) and STDV5 = horizontal or downsloping ST depression (mm) in V5. A logit probability > or = 0 identified CAD with a sensitivity of 79% and a specificity of 89%. The model correctly identified 28/36 (78%) patients with CAD, and 7/10 (70%) patients with NCA (correct diagnosis 76%; p < 0.02) in a separate random group of 46 unselected patients with positive exercise tests undergoing diagnostic coronary angiography.

Dobutamine stress echocardiography (DSE) and exercise thallium-201 single-photon emission computed tomography (SPECT) were compared for the accuracy in detecting coronary artery disease (CAD) in 51 consecutive patients. Twenty-six (group 1) of the 51 patients achieved adequate exercise end points, and 25 (group 2) did not. There were 38 patients with angiographically documented CAD. The overall sensitivity of DSE and thallium-201 SPECT in detecting CAD was 92 and 76% (p = NS), and the specificity was 77 and 77% (p = NS), respectively. The sensitivity of DSE is the same as that of SPECT in group 1 (90 vs. 90%; p = NS) and higher than that of SPECT in group 2 (94 vs. 61%; p < 0.05). In patients with CAD without a history of acute myocardial infarction or pathological Q wave on resting electrocardiogram, the sensitivity of DSE is the same as that of SPECT in group 1 (82 vs. 82%; p = NS) and also higher than that of SPECT in group 2 (90 vs. 40%; p = 0.03). The sensitivity in detecting individual coronary artery lesions with DSE and thallium-201 SPECT was not affected by the exercise level. The agreement between DSE and thallium SPECT in detecting patients with CAD was 88% in group 1 (kappa = 0.69; p < 0.001) and 76% in group 2 (kappa = 0.45; p = 0.01). The agreement in detecting vascular territories with ischemia was 68% in group 1 (kappa = 0.30; p < 0.01) and 75% in group 2 (kappa = 0.33; p < 0.001). The agreement in detecting vascular territories with a scar was 87% in group 1 (kappa = 0.55; p < 0.001) and 85% in group 2 (kappa = 0.44; p < 0.001). In conclusion, the sensitivity and specificity of DSE in detecting CAD are similar to that of thallium-201 SPECT with an exercise level > or =85% of the maximal predicted heart rate. However, in patients who cannot exercise adequately, DSE is more accurate than thallium SPECT. The agreement between DSE and thallium SPECT in detecting patients with CAD and identifying ischemia of individual vascular territories is also affected by the exercise level.

Acute coronary syndromes are defined as unstable angina, non-Q-wave myocardial infarction, and Q-wave myocardial infarction. These entities remain among the commonest life-threatening illnesses in industrialized nations. Prompt recognition of a patient with an acute coronary syndrome is important since appropriate therapy can markedly improve the patient's prognosis. Reperfusion strategies for patients with Q-wave myocardial infarction, and anticoagulation and antiplatelet therapy for patients with unstable angina or non-Q-wave myocardial infarction are examples of such potentially life-saving interventions. A number of adjunctive pharmacological interventions are also beneficial following reperfusion therapy in patients with Q-wave myocardial infarction. Management of Complications following Q-wave myocardial infarction has improved markedly in recent years. This is particularly the case with postinfarction ischemia or heart failure. Persistent arrhythmias, and in particular ventricular arrhythmias, remain a troubling challenge for the clinician. Reperfusion therapy markedly reduces the incidence of complications following Q-wave myocardial infarction.

We studied the ability to predict depressed left ventricular ejection fraction (LVEF) from clinical and exercise test findings prior to surgery in consecutive patients who underwent coronary artery bypass grafting (CABG) from 1988 to 1991 (n = 663). Multivariate analysis showed a history of myocardial infarction, pathological Q-wave in resting ECG, systolic blood pressure at maximal exercise and the degree of mitral regurgitation as significant independent predictors of impaired LVEF. The relative risk (RR) of depressed LVEF was markedly increased for a previous history of myocardial infarction (RR 3.3, p < 0.0001) and a pathological Q-wave in resting ECG (RR 2.4, p < 0.0001). All associations found between depressed LVEF and exercise test results were poor, and of little value for discriminating patients with depressed LVEF. Thus, clinical data appear to be better markers of low LVEF than the information obtained from the exercise test.

To determine the role of the sinus node artery and the clinical course in postmyocardial infarction sinus node dysfunction, 27 patients with acute inferior myocardial infarction and single-vessel coronary artery disease were studied. In 13 patients (group 1) the infarct-related coronary artery was occluded proximally and in 14 (group 2) distally to the site of origin of the sinus node artery. At electrophysiology, performed 10 +/- 3 days from the acute event, basal and intrinsic heart rate were lower in group 1 compared to group 2 patients (54 +/- 4.8 vs. 69 +/- 7 beats/min, p = 0.001, and 66 +/- 7 vs. 76 +/- 8 beats/min, p = 0.006, respectively) while basal and intrinsic corrected sinus node recovery times were prolonged in group 1 compared to group 2 patients (585 +/- 49.3 vs. 324 +/- 61.3 ms, p = 0.0001, and 601 +/- 39.1 vs. 335 +/- 73 ms, p = 0.0001). During a 6-month follow-up no episodes of dizziness, syncope or angina were reported. Moreover, at the end of follow-up resting heart rate (70 +/- 11 vs. 73 +/- 7 beats/min, nonsignificant), maximal exercise heart rate (166 +/- 19 vs. 170 +/- 23 beats/min, nonsignificant), and exercise time (491 +/- 120 vs. 480 +/- 155 s, nonsignificant) were similar between the two groups and no exercise-induced ischemic ST segment depression was observed. Sinus node dysfunction in patients with inferior myocardial infarction and one-vessel disease is related to the occlusion of the infarct-related coronary artery proximal to the site of origin of the sinus node artery and is not associated with increased cardiovascular morbidity in the first 6 months from the acute event.

The diagnostic values of adenosine, dobutamine, and exercise radionuclide ventriculography (RNVG) in the detection of coronary artery disease (CAD), and the characteristics of those patients who showed myocardial ischemia during the infusion of adenosine or dobutamine were assessed in 41 patients with suspected CAD. Sensitivity, specificity, and accuracy, respectively, for detecting patients with CAD were 35 (p < 0.01 vs. exercise RNVG), 100 and 46% (p < 0.01 vs. exercise RNVG) with adenosine RNVG, 74, 100 and 78% with dobutamine RNVG and 88, 71 and 85% with exercise RNVG. There was a significant difference in physiologic parameters during the provocation of ischemia by adenosine versus exercise RNVG, although these parameters were similar by dobutamine and exercise RNVG. Stepwise discriminant analysis revealed that the number of stenotic vessels was an important and independent predictor for the myocardial ischemia induced by each stress; the peak filling rate was the only predictor for adenosine-induced ischemia. Dobutamine induced myocardial ischemia in a way similar to that of exercise, and was more useful than adenosine for pharmacologic stress RNVG. The mechanism of the adenosine-induced ischemia seemed to differ from that of the ischemia induced by dobutamine or exercise, and to be closely associated with left ventricular diastolic function.

This study was undertaken to determine the prevalence and distribution of diastolic function abnormalities at rest and during isometric exercise in patients with systemic hypertension using the recently introduced handgrip-apexcardiographic test (HAT). It has been shown that HAT reflects left ventricular pressure changes in early (relaxation) and late (compliance) diastole. A HAT was obtained in 132 patients with systemic hypertension (duration >1 year) without history of congestive heart failure. A healthy group (n = 186) served as control subjects. Diastolic abnormalities were present at rest in 53/132 (40%) and during isometric handgrip stress in 92/132 (70%) patients. At rest the most frequent diastolic abnormality was the prolongation of relaxation time (27%) whereas an isolated increase in A wave was rare (8%). During isometric exercise, however, an elevation of A wave was the predominant abnormality (38%) whereas an isolated prolongation of relaxation time was less frequent (14%). Alternatively, an 'ischemic' pattern (abnormal prolongation of resting normal relaxation time during handgrip and/or abnormal as well as more than double increase of resting normal relative A wave to total height during or after handgrip) was observed in 29%. In 89% of these patients with an ischemic pattern of diastolic changes, a typical angina and/or positive stress ECG and/or angiographically proved coronary artery disease were present. Using HAT data the present study demonstrates for the first time that in patients with systemic hypertension: (1) diastolic abnormalities occur significantly more frequently during isometric stress than at rest, (2) the most frequently observed diastolic abnormality at rest is the relaxation time prolongation whereas during isometric stress the A wave elevation, and (3) patients with an ischemic pattern of exercise-induced diastolic abnormalities show frequently clinical or angiographic evidence of demand ischemia. Thus, HAT can become a useful additional diagnostic tool for detecting latent diastolic dysfunction and myocardial ischemia in this clinical setting.

The finding of elevated levels of creatine kinase (CK) and its myocardial isoenzyme (CK MB) in the blood of patients with acute chest pain syndromes is a key factor in making the diagnosis of acute myocardial infarction. With the widespread use of thrombolytic therapy and emergency angioplasty, the ability to make a rapid and accurate diagnosis of myocardial infarction is critical. A new rapid method for analysis of the subforms of the MB isoenzyme has been shown to be sensitive and specific for the diagnosis of myocardial infarction in the general population. Because of its rapidity it has been replacing standard analyses of total CK and CK MB in some centers in guiding the initial therapy of patients with chest pain. Levels of CK MB can be abnormally elevated in hemodialysis patients even in the absence of acute myocardial necrosis. This study was undertaken in order to determine if subform analysis of the MB isoenzyme could similarly be abnormal in hemodialysis patients without acute coronary syndromes. CK MB subforms were analyzed in 52 patients without any recent cardiac symptoms who came into the dialysis unit for a routine hemodialysis treatment. We then applied the same criteria for the diagnosis of an acute myocardial infarction as would be used clinically. In this population, the subform analysis was surprisingly consistent with myocardial infarction in approximately 29% of the patients. Thus, subform analysis appears likely to result in an erroneous diagnosis of acute myocardial infarction in patients on hemodialysis.

In this essay we review data on absolute quantitation of myocardial blood flow (MBF) in humans. Earlier work established that coronary heart disease (CAD) can be detected by coronary angiography and that this disease has characteristic features at rest and during stress, which indicate the linkage between regional metabolic needs and myocardial perfusion. In the 1970s myocardial perfusion was mapped in patients with radioxenon, but this method had significant technical limitations. About the same time, radioactive microspheres were introduced for cardiovascular research and investigations; these particles provided insights on MBF in acute infarction and ischemia, myocardial reperfusion, collateral circulation, myocardial blood flow during exercise, coronary flow reserve (CFR), and layer-to-layer distribution of MBF. Studies with microspheres also permitted investigators to establish the presence in the heart of MBF heterogeneity. Currently, there are several techniques that aim at extending these concepts into clinical investigation. Two of these techniques, i.e. Doppler coronary flow velocity and fast magnetic resonance imaging assess epicardial flow dynamics and CFR. Contrast myocardial echocardiography is another novel technique which has been useful in mapping the area at risk, reperfusion, myocardial viability and collateral circulation. This essay also considers the emerging technique of intracoronary ultrasound which has shown evidence of disease underestimation by conventional contrast angiography. Positron emission tomography (PET) is a noninvasive technique that uniquely and quantitatively maps myocardial perfusion and CFR. The latter can be computed before and after angioplasty. PET studies have further demonstrated that chronic myocardial ischemia does not exist as a distinct state in patients with CAD. From the above investigations the concept has arisen that not only is CAD an entity involving epicardial vessels but also, in a significant portion of patients, an abnormal microcirculation plays an important role in the pathogenesis of ischemic syndromes. PET studies have relatively low spatial resolution since they cannot resolve layer-to-layer absolute MBF.

This review discusses the applications of MRI to quantification of the myocardial perfusion. The first step of the measurement is to obtain a concentration-time curve from a signal intensity-time (SI) curve. Factors which influence the correlation between SI and the concentration are discussed for relaxivity and susceptibility agents. The second stage of measurement is to extract parameters of myocardial perfusion from the concentration-time curve. Two methods are considered, one for an intravascular agent and the other for an extravascular agent. Key points are illustrated with experimental data.

Coronary artery fistula is a very rare congenital malformation with an abnormal coronary-cameral communication that may involve any chamber and any or all coronary artery branches. We present our experience with 11 consecutive patients (mean age 16.6 years, ranging from 4 to 64 years); 9 of them were treated surgically, spontaneous closure of the fistula was observed in 1 patient and 1 patient is still under observation. Nine patients were under 17 years of age at the time of operation whereas only 2 patients were older (56 and 64 years). Fistulas originated from the right coronary artery in 4 patients and drained either into the right (n = 3) or into the left system (n = 1). In 8 patients, the origin of the coronary artery from the aorta was normal and the fistulous communications developed with the right cardiac structures only. In 2 patients, both coronary arteries were involved in the pathological drainage and 2 patients were demonstrated to have multiple drainage from the left coronary artery. Additional congenital cardiac malformations were found in 2 patients: severe tricuspid valve regurgitation in 1 and ventricular septal defect in another patient. Surgical closure of the fistula was successful in all operated patients (in 1 case treatment was possible without cardiopulmonary bypass). Simple ligation of the fistula was performed in 1 patient, intracardiac closure of the fistula was combined with different reconstructive procedures in the other patients. No hospital mortality nor severe complications occurred in this small group of patients. The mean follow-up interval was 39.4 months and all patients were in NYHA functional class I, except 1 with moderate tricuspid and mitral valve regurgitation. In the presence of symptoms of congestive heart failure, significant left-to-right shunt and arrhythmias, elective closure of coronary fistula is generally accepted, whereas the indication is more controversial in asymptomatic patients. Considering the low perioperative morbidity, we recommend surgical closure of coronary fistulas with significant shunt and/or increased coronary artery diameter.

The aim of this study was to investigate if provoked myocardial ischemia induces increased beat-to-beat QRS amplitude variability in patients with angiographically verified coronary artery disease. 15 patients (median age 62 years, range 46-73 years) and 10 healthy controls (median age 25 years, range 22-42 years) were studied. Dobutamine was infused intravenously at a low and at a high dose. The mean low dose of the drug was 10.0 micrograms/kg/min for both patients and controls, whereas the mean maximum dose was 31 +/- 2 for patients and 38 +/- 1 microgram/kg/min for controls. The total QRS amplitude beat-to-beat variance from 12 leads as well as individual variance scores in each single lead were evaluated. Before infusion, the total QRS variance did not differ between patients and controls, nor did the individual variance in 9 of the 12 ECG leads. Dobutamine elicited an increase (p < 0.01) in the total QRS variance, with significantly higher (p < 0.001) total variance in patients than in controls. At the high dose of the drug, the patients displayed significantly higher individual variance values in each ECG lead as well. During dobutamine infusion, 7 of 15 patients developed ST depressions (> or = 0.1 mV in > or = 2 leads) in 12-lead ECG readings. Eleven of 15 patients developed chest pain (grade > or = 3 at the Borg's CR-10 scale). In conclusion, in patients with ischemic heart disease, dobutamine-provoked stress gives rise to increased QRS amplitude beat-to-beat variability, as a sign of electrical instability of the myocardium.

Dobutamine stress echocardiography has become widely accepted as a safe, reliable and cost effective modality for the evaluation of patients with suspected myocardial ischemia or for prognostic stratification and outcome assessment in patients with known coronary artery disease. while the benefits of this means of cardiovascular testing are very clearly apparent, it is important to understand and recognize possible complications. This paper discusses the occurrence of sustained, nonischemic ventricular tachycardia during dobutamine stress echocardiography in the absence of functional, physiologic or anatomic evidence of coronary artery disease or cardiomyopathy.