Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Estimates for the acoustical stimulation and heating of multiphase biotissue.

Low-intensity, unfocused, ultrasound-induced diathermy can produce undesired temperature increases at the interface of adjacent tissues within the body; particularly, at the interface of soft tissue and bone. This study provides a computational framework for predicting an upper bound on the temperature profile within a multiphase system composed of gel pad (water), tissue and bone from an input of acoustic energy, at frequencies and power levels consistent with applications of therapeutic hyperthermia. The model consists of solving a (one-dimensional) spatially discretized bioheat transfer equation via finite-difference method and updating the solution in time with a forward-Euler scheme. Simulations are then compared to experimental data to determine the energy-to-heat conversion factors within each constituent material using thermocouple-embedded, tissue-mimicking phantom material, with and without bone. Viscous heating artifacts from the presence of the thermocouples in the experimental phantom tissue are accounted for via additional experimental methods similar to those described by Morris et al. (Phys Med Biol 53:4759, 2008). Finally, an example application of the model is presented via prediction of the maximum temperature at the tissue-bone interface, as well as the peak temperatures in the composite structure at the end of a prescribed 2-min sonication, of blood-perfused, human soft-tissue at 1, 2 and 3 MHz frequencies and a spatial peak temporally averaged intensity of [Formula: see text]. The results of this simulation are then related to comparable experimental studies in the literature.

Mobile demersal megafauna at common offshore wind turbine foundations in the German Bight (North Sea) two years after deployment - increased production rate of Cancer pagurus.

Within the next decades the construction of thousands of different types of large wind turbine foundations in the North Sea will substantially increase the amount of habitat available to reef fauna. To gain first insights which effect these substantial changes in habitat structure and diversity might have on faunal stocks settling on hard substrata, we compared the mobile demersal megafauna associated with the common types of wind turbine foundations ('jacket', 'tripod' and 'monopile with scour protections of natural rock') in the southern German Bight, North Sea. Monopiles with scour protection were mostly colonized by typical reef fauna. They were inhabited by an average of about 5000 edible crabs Cancer pagurus (per foundation), which is more than twice as much as found at the foundation types without scour protection. Strong evidence was found that all three foundation types not only function as aggregation sites, but also as nursery grounds for C. pagurus. Assuming equal shares of the three foundation types in future wind farms, we project that about 27% of the local stock of C. pagurus might be produced on site. When, for example, comparing the existing fauna at 1000 ship wrecks and on the autochthonous soft substrate with those which probably will establish at the foundations of 5000 hypothetically realized wind turbines, it becomes clear that the German Bight in the future will provide new artificial reef habitats for another 320% crabs (C. pagurus) and 50% wrasse (Ctenolabrus rupestris) representing substrata-limited mobile demersal hard bottom species. Further research is urgently required in order to evaluate this overspill as it would be an important ecological effect of the recent offshore wind power development.

Supraventricular tachyarrhythmias after hematopoietic stem cell transplantation: incidence, risk factors and outcomes.

Recent studies suggest that cancer patients may be at increased risk for supraventricular tachyarrhythmias (SVTA). We have observed clinically significant SVTA in patients undergoing hematopoietic stem cell transplantation occurring at a median of 6 days post transplant, manifesting as atrial fibrillation/flutter or regular narrow-complex tachycardia and persisting for a median of 3 days (range, 0-8). All patients received aggressive medical therapy and/or electrical cardioversion to restore sinus rhythm and to re-establish hemodynamic stability. Non-Hodgkin's lymphoma (NHL) was the most common diagnosis (53%), and a case control analysis in those patients demonstrated that SVTA occurred in 12% of patients and was associated with older age and pre-existing cardiac conditions. In conclusion, patients undergoing HSCT are at moderate risk for developing SVTA, particularly older patients with a diagnosis of NHL. These arrhythmias are clinically significant, and are a marker for increased mortality and prolonged hospital stay. Additional studies are needed to identify high-risk patients who may benefit from prophylactic anti-arrhythmic therapy.

Risk stratification after successful coronary revascularization: the lack of a role for routine exercise testing.

OBJECTIVE: The objective of this study was to evaluate the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for exercise testing (EXT) after successful coronary revascularization (CR) using the Bypass Angioplasty Revascularization Investigation experience. BACKGROUND: The ACC/AHA guidelines state that EXT within three years of successful CR is not useful. METHODS: The 1,678 patients randomized to CR by either angioplasty or bypass surgery were required to take symptom-limited treadmill tests one, three and five years after revascularization. RESULTS: Patients who took the test at each specified time had a much lower subsequent two-year mortality than those who did not (1.9% vs. 9.4%, 3.5% vs. 12.6% and 3.3% vs. 11.0% at one, three and five years, respectively, after CR [p < 0.0001 for each]). Exercise parameters at the one- and three-year test did not improve a multivariable model of survival after including clinical parameters. Exercising to Bruce stage 3 or generating a Duke score >-6 were independently predictive of two-year survival after the five-year test. ST depression on the one-year test was associated with more revascularizations (relative risk = 1.6; p < 0.001). CONCLUSIONS: Patients with stable multivessel coronary disease who took a protocol-mandated exercise test at one, three and five years after revascularization were at low risk for mortality in the two years subsequent to each test. Exercise parameters did not improve prediction of mortality in the two years after the one- and three-year tests. The ACC/AHA guidelines on exercise testing after CR (no value for routine testing in stable patients for three years after revascularization) are supported by these results.

The effects of contemporary use of coronary stents on in-hospital mortality. Registry Committee of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the effect of coronary stents on in-hospital mortality. BACKGROUND: Despite extensive use of stents for percutaneous coronary interventions (PCIs), their effect on serious in-hospital events, especially mortality, is not well defined. METHODS: A cohort study was performed using 16,811 consecutive native-vessel PCI procedures performed on patients in the Society for Cardiac Angiography & Interventions Registry from July 1, 1996, through December 31, 1998. Patients undergoing balloon-only angioplasty were compared with those receiving a planned or unplanned stent. Procedures with other devices were excluded. Multivariable analyses adjusted for detailed clinical characteristics and for individual laboratory. RESULTS: Stents were associated with a significant reduction in in-hospital mortality (0.3%) compared with balloon procedures (0.6%; multivariable odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34, 0.89; p = 0.014). The risk of emergency coronary bypass also was reduced by stenting (0.3% vs. 0.7%; multivariable OR 0.47; 95% CI: 0.29, 0.76; p = 0.002). Adjustment for the use of glycoprotein IIb/IIIa inhibitors did not change the results, and the effects of stenting relative to balloon procedures were similar in those procedures with and without glycoprotein IIb/IIIa blockade (p = 0.94). CONCLUSIONS: This study suggests that coronary stenting, compared with balloon procedures, reduces in-hospital mortality, independent of the clinical setting.

Effect of smoking on lipid and thrombogenic factors two months after acute myocardial infarction.

Cigarette smoking is linked to increased cardiac morbidity and mortality, and has been shown to affect both lipid profiles and thrombotic factors in healthy subjects. However, the influence of smoking on the atherothrombotic environment has not been studied in a large population of patients after acute myocardial infarction (AMI). Blood samples and medical history, including smoking status, were obtained from 1,045 patients at a 2-month visit after AMI. Smokers were asked to refrain 24 hours before the visit, but not all complied. Measurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein-B, apolipoprotein-A, triglycerides, factor VII, factor VIIa, von Willebrand factor, D-dimer, and plasminogen activator inhibitor. There were 247 current, 443 past, and 349 nonsmokers. After adjustment for clinical variables, current smokers had higher levels of total cholesterol and apolipoprotein-B than past and nonsmokers (p <0.01). High-density lipoprotein cholesterol and apolipoprotein-A levels were similar between groups. Fibrinogen was elevated in current (p = 0.001) and past (p = 0.029) smokers, compared with nonsmokers. Smokers who smoked within 24 hours of blood sampling had higher apolipoprotein-B (p = 0.005), total cholesterol (p = 0.001), and fibrinogen (p = 0.015) levels than those who refrained from smoking. In conclusion, postinfarction patients, who historically have higher levels of atherogenic lipids than healthy subjects, have increased levels of these lipids attributed to active smoking. After smoking cessation, lipid profiles approach nonsmoker levels, but fibrinogen remains elevated. Smoking within 24 hours of blood sampling was associated with further adverse prothrombotic and lipogenic effects.

Association between new electrocardiographic abnormalities after coronary revascularization and five-year cardiac mortality in BARI randomized and registry patients.

There are few data comparing the relative frequency of new electrocardiographic (ECG) abnormalities after coronary artery bypass grafting (CABG) compared with percutaneous transluminal coronary angioplasty (PTCA) and their association with long-term cardiac mortality. The study population consisted of 3,373 patients who were either randomized or eligible to be randomized to CABG or PTCA in the BARI trial. The frequency of new postprocedural ECG abnormalities was significantly greater after a CABG procedure than after PTCA. The incidence of new postprocedural major Q waves, ST-segment elevation, and T-wave abnormalities were significantly more frequent after CABG. After PTCA (n = 1,869), the 5-year cardiac mortality rates associated with the new development of major Q waves, ST-segment elevation, ST-segment depression, T-wave abnormalities, or no abnormality was 18.1%, 8.5%, 8.9%, 6.0%, and 5.4%, respectively. After CABG (n = 1,427), 5-year cardiac mortality rates were 8.0%, 4.2%, 3.8%, 2.8%, and 3.7%, respectively. The adjusted relative risk of 5-year cardiac mortality for new Q-wave abnormalities was 2.6 after CABG (p <0.04) and 4.6 after PTCA (p <0.01). Thus, patients who undergo CABG have more postinitial procedural ECG abnormalities than patients who undergo PTCA. Cardiac mortality is significantly increased by the new development of postprocedural Minnesota code Q-wave abnormalities regardless of whether patients undergo CABG or PTCA.

Long-term clinical outcome in the Bypass Angioplasty Revascularization Investigation Registry: comparison with the randomized trial. BARI Investigators.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation (BARI) included 4039 patients with multivessel coronary artery disease; 1829 consented to randomization, and 2010 did not but were followed up in a registry. Thus, we can evaluate the outcome of physician-guided versus random assignment of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG). METHODS AND RESULTS: We compared the baseline features and outcomes for PTCA and CABG in the overall registry and its predesignated subgroups. We assessed the impact of treatment by choice versus random assignment by comparing the results in the registry with those of the randomized trial. Statistical adjustments for differences in baseline characteristics were made. Within the registry, nearly twice as many patients were selected for PTCA (1189) as CABG (625); mortality at 7 years was similar for PTCA (13.9%) and CABG (14.2%) (P=0.66) before and after adjustment for baseline differences between patients selected for PTCA versus CABG (adjusted RR, 1.02; P=0.86). In contrast to the randomized trial, the 7-year mortality rate of treated diabetics in the registry was equally high (26%) with PTCA or CABG. Seven-year mortality was higher for patients undergoing PTCA in the randomized trial than in the registry (19.1% versus 13.9%, P<0.01) but not for those undergoing CABG (15.6% versus 14.2%, P=0.57). The adjusted relative mortality risk for PTCA in the randomized versus registry population was 1.17 (P=0.16). CONCLUSIONS: BARI physicians were able to select PTCA rather than CABG for 65% of registry patients who underwent revascularization without compromising long-term survival either in the overall population or in treated diabetics.

A simplified lesion classification for predicting success and complications of coronary angioplasty. Registry Committee of the Society for Cardiac Angiography and Intervention.

In 1988, the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures presented a classification of coronary lesions utilizing 26 lesion features to predict the success and complications of balloon angioplasty. Using data from the Registry of the Society for Cardiac Angiography and Interventions (SCAI) we evaluated the ability of this classification to predict success and complications. Lesion success, death in hospital, emergency cardiac bypass surgery, and major adverse events were evaluated in 41,071 patients who underwent single-vessel angioplasty from January 1993 to June 1996. Logistic models using the ACC/AHA lesion classification, vessel patency, or both, were compared. A new classification based on the interaction of the ACC/AHA classification plus lesion patency was compared with the existing ACC/AHA classification. Vessel patency, added to the ACC/AHA classification, improved prediction of lesion success (p

Contemporary trends in coronary intervention: a report from the Registry of the Society for Cardiac Angiography and Interventions.

This report of the Registry for the Society for Cardiac Angiography and Interventions provides data on the trends in coronary interventional procedures from the time period June 1966 through December 1998. A total of 19,510 consecutive coronary interventional procedures were recorded. Over this time period, significant trends in coronary stent implantation were recorded along with a decreasing reliance on balloon angioplasty as sole therapy. Patients with acute myocardial infarction comprised an increased fraction of all procedures. Almost half of all interventions were performed in patients with multivessel disease. Finally, decreasing rates of in-hospital death and emergent bypass surgery compared to prior reports from the registry characterize the current practice of interventional cardiology. Cathet. Cardiovasc. Intervent. 49:19-22, 2000.

Thrombogenic factors and recurrent coronary events.

BACKGROUND: Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. METHODS AND RESULTS: We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. CONCLUSIONS: Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients.

Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Aypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. METHODS AND RESULTS: Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6. 0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. CONCLUSIONS: BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Identification of variables needed to risk adjust outcomes of coronary interventions: evidence-based guidelines for efficient data collection.

OBJECTIVES: Our objectives were to identify and define a minimum set of variables for interventional cardiology that carried the most statistical weight for predicting adverse outcomes. Though "gaming" cannot be completely avoided, variables were to be as objective as possible and reproducible and had to be predictive of outcome in current databases. BACKGROUND: Outcomes of percutaneous coronary interventions depend on patient risk characteristics and disease severity and acuity. Comparing results of interventions has been difficult because definitions of similar variables differ in databases, and variables are not uniformly tracked. Identifying the best predictor variables and standardizing their definitions are a first step in developing a universal stratification instrument. METHODS: A list of empirically derived variables was first tested in eight cardiac databases (158,273 cases). Three end points (in-hospital death, in-hospital coronary artery bypass graft surgery, Q wave myocardial infarction) were chosen for analysis. Univariate and multivariate regression models were used to quantify the predictive value of the variable in each database. The variables were then defined by consensus by a panel of experts. RESULTS: In all databases patient demographics were similar, but disease severity varied greatly. The most powerful predictors of adverse outcome were measures of hemodynamic instability, disease severity, demographics and comorbid conditions in both univariate and multivariate analyses. CONCLUSIONS: Our analysis identified 29 variables that have the strongest statistical association with adverse outcomes after coronary interventions. These variables were also objectively defined. Incorporation of these variables into every cardiac dataset will provide uniform standards for data collected. Comparisons of outcomes among physicians, institutions and databases will therefore be more meaningful.

Importance of exercise capacity in the interpretation of a myocardial ischemic response to exercise testing. Multicenter Study of Myocardial Ischemia Group (MSMI).

Patients who were stable 1 to 6 months after a cardiac event underwent routine exercise testing with thallium scintigraphy. The prognosis of patients with good exercise capacity (Bruce stage 3) was similar whether or not ischemia was demonstrated and similar to patients with reduced exercise capacity and no ischemia, whereas the presence of both ischemia and a reduced exercise tolerance identified patients with a significantly poorer prognosis.

Diagnosis and prognosis of silent ischemia.

Patients with coronary disease react differently to ischemia. Some (types I and II) experience no symptoms, while most patients with silent ischemia have both symptomatic and asymptomatic ischemia. The best evidence suggests that prognosis is determined by the amount of ischemia, not its presentation. In addition, in these patients, silent ischemia during daily living is not common. Prospective prognostic studies have not been performed in patients who do not experience angina with ischemia, therefore treatment must be individualized in these patients, considering the lack of a "warning system".

Risk of major complications from coronary angioplasty performed immediately after diagnostic coronary angiography: results from the Registry of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the risk of performing percutaneous transluminal coronary angioplasty (PTCA) at the time of diagnostic catheterization ("combined procedures"). BACKGROUND: Health care providers are under increasing pressure to combine diagnostic and interventional coronary procedures to reduce costs. However, the risk associated with combined procedures has not been rigorously assessed. METHODS: A multicenter cohort study of 35,700 patients undergoing elective PTCA from 1992 through 1995 was performed to determine the risk of major complications (myocardial infarction, emergency coronary artery bypass graft surgery or death) from combined relative to staged procedures (i.e., performing PTCA at a session subsequent to diagnostic catheterization). RESULTS: The risks of major complications from combined and staged procedures were 2.0% and 1.6%, respectively (unadjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.05 to 1.57). After adjusting for clinical and angiographic differences and clustering by laboratory, the risk from combined procedures was not significantly elevated (multivariable OR 1.18, 95% CI 0.89 to 1.55). However, several subgroups of patients did have an increased risk from combined procedures: patients with multivessel disease (multivariable OR 1.64, 95% CI 1.13 to 2.39); women (multivariable OR 1.64, 95% CI 1.05 to 2.55); patients > 65 years old (multivariable OR 1.40, 5% CI 1.02 to 1.93); and patients undergoing multilesion PTCA (multivariable OR 1.53, 95% CI 1.06 to 2.21). The risk of combined relative to staged procedures decreased over the 4-year period (multivariable p = 0.029). CONCLUSIONS: Combining PTCA with diagnostic catheterization appears to be safe in many patients. However, several subgroups of patients may be at increased risk. Careful patient selection will most likely remain critical to ensuring the safety of combined procedures.

Predictors of success and major complications for primary percutaneous transluminal coronary angioplasty in acute myocardial infarction. An analysis of the 1990 to 1994 Society for Cardiac Angiography and Interventions registries.

OBJECTIVES: The purpose of this study was to determine predictors of successful coronary angioplasty for acute myocardial infarction (MI) and associated predictors of the major complications of in-hospital mortality and emergency coronary artery bypass graft surgery. BACKGROUND: Primary angioplasty is being increasingly used to treat acute MI, but factors affecting the success and major complications have not been well studied. Forty laboratories have been contributing clinical and procedural data to the Society of Cardiac Angiography and Interventions (SCA&I) on primary angioplasty for acute MI. METHODS: Univariable and stepwise multivariable logistic regression analysis of clinical and procedural variables was used to calculate predictors of success and major complications. RESULTS: There were 4,366 primary angioplasty procedures reported from 1990 through 1994, with an overall success rate of 91.5%, an in-hospital mortality rate of 2.5% and a rate of emergency surgery of 4.3%. Higher laboratory primary angioplasty volume and lower age were predictive of success. An intraaortic balloon pump in place, cardiogenic shock and a moribund condition had negative predictive effects. Unsuccessful angioplasty, cardiogenic shock or a moribund state were predictive of in-hospital death. Unsuccessful angioplasty, the absence of a history of hypertension and the absence of congestive heart failure were predictive of emergency surgery. CONCLUSIONS: The rates of success and major complications in the SCA&I Registry are similar to other series. Predictors of success and major complications can be assessed and may be useful for risk stratifying candidates for primary angioplasty in acute MI.

Angina pectoris after recovery from an acute coronary event--the role of psychological factors in Japanese vs North American patients.

To determine whether specific psychological characteristics are associated with angina pectoris in clinically stable patients 1 to 6 months after recovery from an acute coronary event, a battery of tests was administered to 92 Japanese and 646 North American participants (22% females) in the Multicenter Study of Myocardial Ischemia. Of these 738 patients, 541 had originally suffered acute myocardial infarction, 188 had unstable angina, and 9 were admitted for other acute ischemic events. At the time of enrollment, an average of 2.7 months after the index event, 205 patients reported having had anginal symptoms during the preceding months. Compared to those who did not report angina, these patients scored higher on a modified Autonomic Perception Questionnaire (p = 0.04) and lower on the Internal Health Locus of Control Scale (p = 0.004). These differences were generalized across the Japanese and North American cohorts. These results indicate that in these patients, angina pectoris was associated with an increased awareness of a wide range of physical symptoms and a decreased sense of personal control over one's own health and prognosis.