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Background: Galectin-3 (Gal-3) is implicated in cardiac fibrosis, but its association with adverse outcomes after myocardial infarction (MI) is unknown., Objectives: The purpose of this study was to examine the prognostic value of Gal-3 in a community cohort of incident MI., Methods: A population-based incidence MI cohort was prospectively assembled in Olmsted County, Minnesota, between 2002 and 2012. Gal-3 levels were measured at the time of MI. Patients were followed for heart failure (HF) and death., Results: A total of 1,342 patients were enrolled (mean age 67.1 years; 61.3% male; 78.8% non-ST-segment elevation MI). Patients with elevated Gal-3 were older and had more comorbidities. Over a mean follow-up of 5.4 years, 484 patients (36.1%) died and 368 (27.4%) developed HF. After adjustment for age, sex, comorbidities, and troponin, patients with Gal-3 values in tertiles 2 and 3 had a 1.3-fold (95% confidence interval [CI]: 0.9-fold to 1.7-fold) and a 2.4-fold (95% CI: 1.8-fold to 3.2-fold) increased risk of death, respectively (p trend  < 0.001) compared with patients with Gal-3 values in tertile 1. Patients with Gal-3 values in tertiles 2 and 3 had a higher risk of HF with hazard ratios of 1.4 (95% CI: 1.0 to 2.0) and 2.3 (95% CI: 1.6 to 3.2), respectively (p trend  < 0.001). With further adjustment for soluble suppression of tumorigenicity-2, elevated Gal-3 remained associated with increased risk of death and HF. The increased risk of HF did not differ by HF type and was independent of the occurrence of recurrent MI., Conclusions: Gal-3 is an independent predictor of mortality and HF post-MI. These findings suggest a role for measuring Gal-3 levels for risk stratification post-MI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is associated with excess morbidity and mortality for which noncardiac causes are increasingly recognized. The authors previously described an increased risk of cancer among HF patients compared with community controls., Objectives: This study examined whether HF was associated with an increased risk of subsequent cancer among a homogenous population of first myocardial infarction (MI) survivors., Methods: A prospective cohort study was conducted among Olmsted County, Minnesota, residents with incident MI from 2002 to 2010. Patients with prior cancer or HF diagnoses were excluded., Results: A total of 1,081 participants (mean age 64 ± 15 years; 60% male) were followed for 5,327 person-years (mean 4.9 ± 3.0 years). A total of 228 patients developed HF, and 98 patients developed cancer (excluding nonmelanoma skin cancer). Incidence density rates for cancer diagnosis (per 1,000 person-years) were 33.7 for patients with HF and 15.6 for patients without HF (p = 0.002). The hazard ratio (HR) for cancer associated with HF was 2.16 (95% confidence interval [CI]: 1.39 to 3.35); adjusted for age, sex, and Charlson comorbidity index; HR: 1.71 (95% CI: 1.07 to 2.73). The HRs for mortality associated with cancer were 4.90 (95% CI: 3.10 to 7.74) for HF-free and 3.91 (95% CI: 1.88 to 8.12) for HF patients (p for interaction = 0.76)., Conclusions: Patients who develop HF after MI have an increased risk of cancer. This finding extends our previous report of an elevated cancer risk after HF compared with controls, and calls for a better understanding of shared risk factors and underlying mechanisms., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the risk of cancer in patients with heart failure (HF) compared with community controls and to determine the impact of cancer post-HF on outcomes., Background: HF is associated with excess morbidity and mortality. Noncardiac causes of adverse outcomes in HF are increasingly recognized, but not fully characterized., Methods: In a case-control study, we compared the history of cancer among community subjects newly diagnosed with HF from 1979 to 2002 to age-, sex-, and date-matched community controls without HF (961 pairs). Individuals without cancer at the index date (596 pairs) were followed for cancer in a cohort design, and the survival of HF patients who developed cancer was assessed., Results: Before the index date, 22% of HF cases and 23% of controls had a history of cancer (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.75 to 1.17). During 9,203 person-years of follow-up (7.7 ± 6.4 years), 244 new cancer cases were identified; HF patients had a 68% higher risk of developing cancer (hazard ratio [HR]: 1.68; 95% CI: 1.13 to 2.50) adjusted for body mass index, smoking, and comorbidities. The HRs were similar for men and women, with a trend toward a stronger association among subjects ≤75 years of age (p = 0.22) and during the most recent time period (p = 0.075). Among HF cases, incident cancer increased the risk of death (HR: 1.56; 95% CI: 1.22 to 1.99) adjusted for age, sex, index year, and comorbidities., Conclusions: HF patients are at increased risk of cancer, which appears to have increased over time. Cancer increases mortality in HF, underscoring the importance of noncardiac morbidity and of cancer surveillance in the management of HF patients., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the mortality risk of patients with coronary artery disease (CAD) based ona combination of body mass index (BMI) with measures of central obesity., Background: In CAD patients, mortality has been reported to vary inversely with BMI (“obesity paradox”). In contrast,central obesity is directly associated with mortality. Because of this bidirectionality, we hypothesized that CAD patients with normal BMI but central obesity would have worse survival compared to individuals with other combinations of BMI and central adiposity., Methods: We included 15,547 participants with CAD who were part of 5 studies from 3 continents. Multivariate stratifiedCox-proportional hazard models adjusted for potential confounders were used to assess mortality risk according to different patterns of adiposity that combined BMI with measures of central obesity., Results: Mean age was 66 years, 60% were men. There were 5,507 deaths over a median follow-up of 2.4 years (IQR: 0.5 to 7.4 years). Individuals with normal weight central obesity had the worst long-term survival: a person with BMI of 22 kg/m2 and waist circumference (WC) of 101 cm had higher mortality than a person with similar BMI but WC of 85 cm (HR: 1.10[95% CI: 1.05 to 1.17]), than a person with BMI of 26 kg/m2 and WC of 85 cm (HR: 1.20 [95% CI: 1.09 to 1.31]), than a person with BMI of 30 kg/m2 and WC of 85 cm (HR: 1.61 [95% CI: 1.39 to 1.86]) and than a person with BMI of 30kg/m2 and WC of 101 cm (HR: 1.27 [95% CI: 1.18 to 1.39), p < 0.0001 for all)., Conclusions: In patients with CAD, normal weight with central obesity is associated with the highest risk of mortality [corrected]., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine among community patients with heart failure (HF) whether pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography was associated with death and improved risk prediction over established factors, using the integrated discrimination improvement and net reclassification improvement., Background: Although several studies have focused on idiopathic pulmonary arterial hypertension, less is known about pulmonary hypertension among patients with HF, particularly about its prognostic value in the community., Methods: Between 2003 and 2010, Olmsted County residents with HF prospectively underwent assessment of ejection fraction, diastolic function, and PASP by Doppler echocardiography., Results: PASP was recorded in 1,049 of 1,153 patients (mean age 76 ± 13; 51% women). Median PASP was 48 mm Hg (25th to 75th percentile: 37.0 to 58.0). There were 489 deaths after a follow-up of 2.7 ± 1.9 years. There was a strong positive graded association between PASP and mortality. Increasing PASP was associated with an increased risk of death (hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.13 to 1.85 for tertile 2; HR: 2.07, 95% CI: 1.62 to 2.64 for tertile 3 vs. tertile 1), independently of age, sex, comorbidities, ejection fraction, and diastolic function. Adding PASP to models including these clinical characteristics resulted in an increase in the c-statistic from 0.704 to 0.742 (p = 0.007), an integrated discrimination improvement gain of 4.2% (p < 0.001), and a net reclassification improvement of 14.1% (p = 0.002), indicating that PASP improved prediction of death over traditional prognostic factors. All results were similar for cardiovascular death., Conclusions: Among community patients with HF, PASP strongly predicts death and provides incremental and clinically relevant prognostic information independently of known predictors of outcomes., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to examine the association of central (waist circumference [WC] and waist-hip ratio [WHR]) and total obesity (body mass index [BMI]) measures with mortality in coronary artery disease (CAD) patients., Background: The question of which measure of obesity better predicts survival in patients with CAD is controversial., Methods: We searched OVID/Medline, EMBASE, CENTRAL, and Web of Science from 1980 to 2008 and asked experts in the field for unpublished data meeting inclusion criteria, in which all subjects had: 1) CAD at baseline; 2) measures of WC or WHR; 3) mortality data; and 4) a minimum follow-up of 6 months., Results: From 2,188 studies found, 6 met inclusion criteria. We obtained individual subject data from 4, adding unpublished data from a cardiac rehabilitation cohort. A variable called "central obesity" was created on the basis of tertiles of WHR or WC. Cox-proportional hazards were adjusted for age, sex, and confounders. The final sample consisted of 15,923 subjects. There were 5,696 deaths after a median follow-up of 2.3 (interquartile range 0.5 to 7.4) years. Central obesity was associated with mortality (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.58 to 1.83), whereas BMI was inversely associated with mortality (HR: 0.64, 95% CI: 0.59 to 0.69). Central obesity was also associated with higher mortality in the subset of subjects with normal BMI (HR: 1.70, 95% CI: 1.52 to 1.89) and BMI ≥30 kg/m(2) (HR: 1.93, 95% CI: 1.61 to 2.32)., Conclusions: In subjects with CAD, including those with normal and high BMI, central obesity but not BMI is directly associated with mortality., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the lifetime burden and risk factors for hospitalization after heart failure (HF) diagnosis in the community., Background: Hospitalizations in patients with HF represent a major public health problem; however, the cumulative burden of hospitalizations after HF diagnosis is unknown, and no consistent risk factors for hospitalization have been identified., Methods: We validated a random sample of all incident HF cases in Olmsted County, Minnesota, from 1987 to 2006 and evaluated all hospitalizations after HF diagnosis through 2007. International Classification of Diseases-9th Revision codes were used to determine the primary reason for hospitalization. To account for repeated events, Andersen-Gill models were used to determine the predictors of hospitalization after HF diagnosis. Patients were censored at death or last follow-up., Results: Among 1,077 HF patients (mean age 76.8 years, 582 [54.0%] female), 4,359 hospitalizations occurred over a mean follow-up of 4.7 years. Hospitalizations were common after HF diagnosis, with 895 (83.1%) patients hospitalized at least once, and 721 (66.9%), 577 (53.6%), and 459 (42.6%) hospitalized > or =2, > or =3, and > or =4 times, respectively. The reason for hospitalization was HF in 713 (16.5%) hospitalizations and other cardiovascular in 936 (21.6%), whereas over one-half (n = 2,679, 61.9%) were noncardiovascular. Male sex, diabetes mellitus, chronic obstructive pulmonary disease, anemia, and creatinine clearance <30 ml/min were independent predictors of hospitalization (p < 0.05 for each)., Conclusions: Multiple hospitalizations are common after HF diagnosis, though less than one-half are due to cardiovascular causes. Comorbid conditions are strongly associated with hospitalizations, and this information could be used to define effective interventions to prevent hospitalizations in HF patients.

Objectives: We sought to compare left ventricular (LV) systolic stiffness and contractility in normal subjects, hypertensive patients without heart failure, and patients with heart failure and preserved ejection fraction (HFpEF) and to determine whether LV systolic stiffness or myocardial contractility is associated with the rate of mortality in patients with HFpEF., Background: Arterial load is increased in patients with hypertension and is matched by increased end-systolic LV stiffness (ventricular-arterial coupling). Increased end-systolic LV stiffness may be mediated by enhanced myocardial contractility or processes that increase passive myocardial stiffness., Methods: Healthy control patients (n = 617), hypertensive patients (no heart failure, n = 719), and patients with HFpEF (n = 244, 96% hypertensive) underwent echo-Doppler characterization of arterial (Ea) and LV end-systolic (Ees) stiffness (elastance), ventricular-arterial coupling (Ea/Ees ratio), and chamber-level and myocardial contractility (stress-corrected midwall shortening)., Results: We found that Ea and Ees were similarly increased in hypertensive patients with or without HFpEF compared with control patients, but ventricular-arterial coupling was similar across groups. In hypertensive patients, increased Ees was associated with enhanced chamber-level and myocardial contractility, whereas in patients with HFpEF, chamber and myocardial contractility were depressed compared with both hypertensive and control patients. Group differences persisted after adjusting for geometry. In patients with HFpEF, impaired myocardial contractility (but not Ees) was associated with increased age-adjusted mortality., Conclusions: Although arterial load is increased and matched by increased LV systolic stiffness in hypertensive patients with or without HFpEF, the mechanisms of systolic LV stiffening differ substantially. These data suggest that myocardial contractility increases to match arterial load in asymptomatic hypertensive heart disease, but that progression to HFpEF may be mediated by processes that simultaneously impair myocardial contractility and increase passive myocardial stiffness.

Objectives: This study sought to define the prevalence, severity, and significance of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) in the general community., Background: Although HFpEF is known to cause PH, its development is highly variable. Community-based data are lacking, and the relative contribution of pulmonary venous versus pulmonary arterial hypertension (HTN) to PH in HFpEF is unknown. We hypothesized that PH would be a marker of symptomatic pulmonary congestion, distinguishing HFpEF from pre-clinical hypertensive heart disease., Methods: This community-based study of 244 HFpEF patients (age 76 +/- 13 years; 45% male) was followed up using Doppler echocardiography over 3 years. Control subjects were 719 adults with HTN without HF (age 66 +/- 10 years; 44% male). Pulmonary artery systolic pressure (PASP) was derived from the tricuspid regurgitation velocity and PH defined as PASP >35 mm Hg. Pulmonary capillary wedge pressure (PCWP) was estimated from the ratio of early transmitral flow velocity to early mitral annular diastolic velocity., Results: In HFpEF, PH was present in 83% and the median (25th, 75th percentile) PASP was 48 (37, 56) mm Hg. PASP increased with PCWP (r = 0.21; p < 0.007). Adjusting for PCWP, PASP was higher in HFpEF than HTN (p < 0.001). The PASP distinguished HFpEF from HTN with an area under the receiver-operating characteristic curve of 0.91 (p < 0.001) and strongly predicted mortality in HFpEF (hazard ratio: 1.3 per 10 mm Hg; p < 0.001)., Conclusions: PH is highly prevalent and often severe in HFpEF. Although pulmonary venous HTN contributes to PH, it does not fully account for the severity of PH in HFpEF, suggesting that a component of pulmonary arterial HTN also contributes. The potent effect of PASP on mortality lends support for therapies aimed at pulmonary arterial HTN in HFpEF.

Objectives: Our aim was to examine whether gender-based differences in mortality after percutaneous coronary interventions (PCIs) have changed in the past 25 years., Background: Women with coronary artery disease have a higher risk of adverse outcomes after PCIs than do men. Recent temporal trends in short-term and long-term mortality in women after PCIs are unknown., Methods: We performed a retrospective cohort study of 18,885 consecutive, unique patients who underwent PCIs between 1979 and 1995 (early group, n = 7,904, 28% women) and between 1996 and 2004 (recent group, n = 10,981, 31% women). Thirty-day and long-term mortality were compared by gender., Results: Compared with men, women undergoing PCIs were older and more likely to have diabetes mellitus, hypertension, or hypercholesterolemia. Overall, PCI was successful in 89% of women and 90% of men. In the recent group, 30-day mortality was significantly reduced compared with that in the early group in women (2.9% vs. 4.4%, p = 0.002) and men (2.2% vs. 2.8%, p = 0.04). However, long-term survival was similar between the early and recent groups among both men and women. After adjustment for risk factors, there was no difference between men and women from 1994 onward for either 30-day or long-term outcomes., Conclusions: The 30-day mortality after PCI in men and women has decreased in the past 25 years. After accounting for baseline risks, no differences in short-term or long-term mortality were observed between men and women.

Objectives: We sought to examine temporal trends in the utilization of coronary revascularization in a geographically defined population., Background: Earlier reports on revascularization utilization focused on inpatient settings and did not distinguish incident from recurrent procedures. Furthermore, little is known on age- and gender-specific trends. Finally, longitudinal data on the utilization and results of coronary angiography as explanatory factors for the changing revascularization practice are lacking., Methods: Data integrating diagnostic and therapeutic coronary procedures performed in Olmsted County (Minnesota) between 1990 and 2004 were analyzed. Standardized rates were calculated applying the direct method and temporal trends compared using Poisson regression models., Results: Revascularization utilization increased by 24% during the study (95% confidence interval [CI] 5% to 46%), but the trends diverged by procedure type, with a sustained increase (69%, 95% CI 43% to 101%) for percutaneous coronary interventions (PCI) contrasting with a stabilization, then decline (-33%, 95% CI -16% to -47%) for coronary artery bypass grafting (CABG). For PCI, although the use increased in all categories, greater increases were noted in the elderly, in women, and for recurrent procedures. No such patterns were detected for CABG. Angiography use remained stable, and the rate of 3-vessel and/or left main disease declined (-22%, 95% CI -8% to -33%)., Conclusions: Over the 15-year period, revascularization increased in the community with a large increase in PCI partially offset by a decrease in CABG. More PCIs are performed in women and the elderly and for recurrent disease. These changes occurred within the context of a decline in multivessel disease and thus likely reflect the natural history of coronary artery disease.

Objectives: We assessed the relationship of season and weather types with myocardial infarction (MI) and sudden cardiac death (SCD) in a geographically defined population, and tested the hypothesis that the increased risk in winter was related to weather., Background: Winter peaks in coronary heart disease (CHD) have been documented. Yet, it is uncertain if seasonality exists for both incident events and deaths, and the role of weather conditions is not clear., Methods: The daily occurrence of incident MI and SCD in Olmsted County was examined with data from the National Weather Service. Poisson regression models were used to assess the relative risks (RRs) associated with season and climatic variables. Subsequent analysis stratified SCD into those with and without antecedent CHD (unexpected SCD)., Results: Between 1979 and 2002, 2,676 MI and 2,066 SCD occurred. The age-, gender-, and year-adjusted RR of SCD, but not of MI, was increased in winter versus summer (1.17, 95% confidence interval [CI] 1.03 to 1.32) and in low temperatures (1.20, 95% CI 1.07 to 1.35, for temperatures below 0 degrees C vs. 18 degrees C to 30 degrees C). These associations were stronger for unexpected SCD than for SCD with prior CHD (p < 0.05). After adjustment for all climatic variables, low temperature was associated with a large increase in the risk of unexpected SCD (RR = 1.38, 95% CI 1.10 to 1.73), while the association with winter declined (RR = 1.06, 95% CI 0.83 to 1.35)., Conclusions: These data suggest that the winter peak in SCD can be accounted for by daily weather.

Objectives: The aim of this study was to examine participation in cardiac rehabilitation after myocardial infarction (MI) by age and gender and the association of participation with survival., Background: Lesser participation in cardiac rehabilitation has been reported for women and the elderly., Methods: All incident MIs in Olmsted County were validated. Baseline characteristics and outcomes were ascertained from the medical record. Logistic regression examined the association between participation, age, and gender. Propensity scores were used to examine the association between participation and outcome., Results: Among 1,821 persons with incident MI (58% men, 46% age >70 years), 55% participated in cardiac rehabilitation. Participants were more likely to be men, younger, and have fewer comorbidities (p < 0.01 for all comparisons). After adjustment, women were 55% less likely to participate than men (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.34 to 0.60), and persons 70 years or older were 77% less likely to participate than persons younger than 60 (OR 0.23, 95% CI 0.16 to 0.33). Participants had a lower risk of death and recurrent MI at three years (p < 0.001 and p = 0.049, respectively). The survival benefit associated with participation was stronger in more recent years (relative risk [RR] for 1998 vs. 1982 0.28, 95% CI 0.18 to 0.43; RR for 1990 vs. 1982 0.41, 95% CI 0.33 to 0.52)., Conclusions: Approximately half of the patients participated in cardiac rehabilitation after MI. Participation did not increase over time. Women and elderly persons were less likely to participate, independently of other characteristics. Participation in rehabilitation was independently associated with decreased mortality and recurrent MI, and its protective effect was stronger in more recent years.

Objectives: The study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD., Background: Persons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes., Methods: Using two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender., Results: In this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD., Conclusions: These findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms.

Objectives: We sought to define the prognostic implications of the extent and severity of exercise echocardiographic abnormalities in patients with good exercise capacity. BACKGROUND; The exercise capacity of patients with known or suspected coronary artery disease (CAD) is of prognostic importance, as is the extent of exercise-related left ventricular (LV) hypoperfusion or dysfunction., Methods: We examined the outcomes of 1,874 patients with known or suspected CAD (mean age 64 +/- 10 years, 64% men) who had good exercise capacity (> or = 5 metabolic equivalents [METs] for women, > or = 7 METs for men) but abnormal exercise echocardiograms and analyzed the potential association between clinical, exercise and echocardiographic variables and subsequent cardiac events., Results: Multivariate predictors of time to cardiac death or nonfatal myocardial infarction (MI) were diabetes mellitus (risk ratio [RR] 1.88; 95% confidence interval [CI] 1.2 to 3.0), history of MI (RR 2.44; 95% CI 1.6 to 3.6) and an increase or no change in LV end-systolic size in response to exercise (RR 1.61; 95% CI 1.1 to 2.5). Using echocardiographic variables that were of incremental prognostic value, we were able to stratify the cardiac risk of the study population; cardiac death or nonfatal MI rate per person-year of follow-up was 1.6% for patients who had a decrease in LV end-systolic size in response to exercise (n = 1,330) and 1.2% for patients who did not have any severely abnormal LV segments immediately after exercise (n = 868)., Conclusions: In patients with good exercise capacity, echocardiographic descriptors of the extent and severity of exercise-related LV dysfunction were of independent and incremental prognostic value. Stratification of patients into low- and higher risk subgroups was possible using these exercise echocardiographic characteristics.

Objectives: This study was designed to determine the effect of gender on the prognostic value of exercise echocardiography., Background: Limited information exists regarding gender differences in prognostic value of exercise echocardiography., Methods: We obtained follow-up (3.2 +/- 1.7 years) in 5,798 consecutive patients who underwent exercise echocardiography for evaluation of known or suspected coronary artery disease., Results: There were 3,322 men (mean age 62 +/- 12 years) and 2,476 women (mean age 62 +/- 12 years) (p = 0.7). New or worsening wall motion abnormalities developed with exercise in 35% of men and 25% of women (p = 0.001). Cardiac events, including cardiac death (107 patients) and nonfatal myocardial infarction (148 patients), occurred in 5.3% of men and 3.1% of women (p = 0.001). Addition of the percentage of ischemic segments to the clinical and rest echocardiographic model provided incremental information in predicting cardiac events for both men (chi(2) = 137 to 143, p = 0.014) and women (chi(2) = 72 to 76, p = 0.046). By multivariate analysis, exercise electrocardiographic and exercise echocardiographic predictors of cardiac events in both men and women were workload and exercise wall motion score index. There was no significant interaction effect of rest echocardiography (p = 0.79), exercise electrocardiography (p = 0.38) or exercise echocardiography (p = 0.67) with gender., Conclusions: Although cardiac events occurred more frequently in men, the incremental value of exercise echocardiography was comparable in both genders. Of all exercise electrocardiographic and exercise echocardiographic variables, workload and exercise wall motion score index had the strongest association with outcome. The results of exercise echocardiography have comparable implications in both men and women.

Objectives: This study examined gender differences and temporal changes in the clinical characteristics of patients referred for nuclear stress imaging, their imaging results and subsequent utilization of coronary angiography and revascularization., Background: Gender bias may influence resource utilization in patients with coronary artery disease (CAD). No study has analyzed gender differences and time trends in patients referred for noninvasive testing and subsequent use of invasive procedures., Methods: Between January 1986 and December 1995, 14,499 patients (5,910 women and 8,589 men) without established CAD underwent stress myocardial perfusion imaging. The clinical characteristics, imaging results, coronary angiograms and revascularization outcomes were compared in women and men over time., Results: The mean pretest probability of CAD was lower in women (45%) than in men (70%) (p < 0.001). More women (69%) than men (42%) had normal nuclear images (p < 0.001). Men (17%) were more likely than women (8%) to undergo coronary angiography (p < 0.001). Male gender was independently associated with referral for coronary angiography (multivariate model: chi-square = 16, p < 0.001) but was considerably weaker than the imaging variables (summed reversibility score: chi-square = 273, p < 0.001). Revascularization was performed in more men (46% of the population undergoing angiography) than women (39%) (p = 0.01), but gender was not independently associated with referral to revascularization. There were no significant differences in clinical, imaging or invasive variables between the genders over time., Conclusions: There was little evidence for a bias against women in this study. Women were somewhat less likely to undergo coronary angiography but were referred for stress perfusion imaging more liberally. Practice patterns remained constant over this 10-year period.

Objectives: We sought to determine the prognostic value of exercise echocardiography in the elderly., Background: Limited data exist regarding the prognostic value of exercise testing in the elderly, a population which may be less able to exercise and is at increased risk of cardiac death., Methods: Follow-up (2.9 +/- 1.7 years) was obtained in 2,632 patients > or = 65 years who underwent exercise echocardiography., Results: There were 1,488 (56%) men and 1,144 (44%) women (age 72 +/- 5 years). The rest ejection fraction was 56 +/- 9%. Rest wall motion abnormalities were present in 935 patients (36%). The mean work load was 7.7 +/- 2.3 metabolic equivalents (METs) for men and 6.5 +/- 1.9 METs for women. New or worsening wall motion abnormalities developed with stress in 1,082 patients (41%). Cardiac events included cardiac death in 68 patients and nonfatal myocardial infarction in 80 patients. The addition of the exercise electrocardiogram to the clinical and rest echocardiographic model provided incremental information in predicting both cardiac events (chi-square = 77 to chi-square = 86, p = 0.003) and cardiac death (chi-square = 71 to chi-square = 86, p < 0.0001). The addition of exercise echocardiographic variables, especially the change in left ventricular end-systolic volume with exercise and the exercise ejection fraction, further improved the model in terms of predicting cardiac events (chi-square = 86 to chi-square = 108, p < 0.0001) and cardiac death (chi-square = 86 to chi-square = 99, p = 0.004)., Conclusions: Exercise echocardiography provides incremental prognostic information in patients > or = 65 years of age. The best model included clinical, exercise testing and exercise echocardiographic variables.

Objective: This study evaluated the incremental value of dobutamine stress echocardiography (DSE) for assessment of cardiac risk before nonvascular surgery., Background: Limited information exists regarding the preoperative assessment of cardiac risk in patients with known or suspected coronary artery disease who are to undergo nonvascular surgery., Methods: All patients (303 men, 227 women) who underwent DSE before nonvascular surgery and did not sustain an intervening event (coronary revascularization or cardiac event) were studied. Clinical, electrocardiographic and rest and stress echocardiographic variables were evaluated to identify predictors of postoperative cardiac events., Results: Events occurred in 6% of patients: 1 cardiac death and 31 nonfatal myocardial infarctions. All of these patients had inducible ischemia on DSE (sensitivity 100%, specificity 63%). Multivariate predictors of postoperative events in patients with ischemia were history of congestive heart failure (p = 0.006; odds ratio = 4.66; confidence interval 1.55 to 14.02) and ischemic threshold less than 60% of age-predicted maximal heart rate (p = 0.0001; odds ratio 7.002; confidence interval 2.79 to 17.61). Clinical variables of Eagle's index identified 21% of patients as low, 68% as intermediate and 11% as high risk preoperatively; the postoperative event rates were 3%, 6%, and 14%, respectively. Dobutamine stress echocardiography identified 60% of patients as low (no ischemia), 32% as intermediate (ischemic threshold 60% or more) and 8% as high risk (ischemic threshold < 60%); postoperative event rates were 0%, 9% and 43%, respectively., Conclusions: In this population of patients with known or suspected coronary artery disease evaluated before nonvascular surgery, DSE had incremental value over clinical, electrocardiographic and rest echocardiographic variables for identifying patients at low, intermediate and high risk for postoperative cardiac events. Ischemia occurring at less than 60% of age-predicted maximal heart rate identified patients at highest risk.

Objectives: We sought to examine the utilization of exercise stress testing in relation to age and gender in a population-based setting., Background: The utilization of noninvasive procedures has been shown to be associated with the subsequent use of invasive procedures. Yet, there are no population-based data on the utilization of stress testing; in particular, although gender differences in the use of invasive procedures have been reported, the use of noninvasive procedures has not been examined in relation to gender., Methods: In Olmsted County, Minnesota, passive surveillance of the medical care of the community is provided through the Rochester Epidemiology Project. A population-based cohort of Olmsted County residents undergoing exercise tests was identified. The medical records of residents with prevalent and incident exercise tests in 1987 and 1988 were reviewed. For persons with an initial test (incidence cohort), data on clinical presentation, test indications and results were abstracted. Stress test utilization rates were calculated, and crude rates were directly adjusted to the age distribution of the 1980 U.S. population. To help interpret patterns of use at the population level, coronary heart disease mortality rates (International Classification of Diseases, 9th revision, codes 410 to 414) were calculated (crude and directly adjusted to the overall age distribution of the 1980 U.S. population) and used as an indicator of coronary disease burden., Results: A total of 2,624 tests were performed. The crude utilization rate (per 100,000) was 1,888 for men and 703 for women (rate ratio for men over women 2.7, 95% confidence interval [CI] 2.5 to 2.9); it remained significantly higher in men across all age strata. The crude incidence rate (per 100,000) of initial stress tests was 1,112 for men and 517 for women (rate ratio 2.2, 95% CI 1.9 to 2.4). For both men and women, the incidence increased with age; however, incidence remained lower in women in all age strata. At the time that they underwent an initial test, women were more symptomatic and had poorer exercise performance than men. The rate ratio of men over women for coronary heart disease mortality was 1.1 (95% CI 0.9 to 1.2). The age-adjusted rate ratios for stress test utilization were 2.8 (95% CI 2.5 to 3.0), and that for coronary heart disease mortality was 1.9 (95% CI 1.7 to 2.2)., Conclusions: These population-based data show that during the study period, the utilization of stress testing in Olmsted County was lower in women than in men. Women in the incidence cohort were older and more symptomatic and had poorer exercise performance than men. Such differences should be considered when examining the utilization of subsequent invasive procedures according to gender.

Objectives: This study sought to examine the outcome of a large group of patients after normal exercise echocardiography and to identify potential predictors of subsequent cardiac events., Background: Earlier studies suggested that prognosis after normal exercise echocardiography is favorable, with a low subsequent cardiac event rate. These studies involved a small number of patients and did not have sufficient statistical power to stratify risk., Methods: The outcomes of 1,325 patients who had normal exercise echocardiograms were examined. End points were overall and cardiac event-free survival. Cardiac events were defined as cardiac death, nonfatal myocardial infarction and coronary revascularization. Patient characteristics were analyzed in relation to time to first cardiac event in a univariate and multivariate manner to determine which, if any, were associated with an increased hazard of subsequent cardiac events., Results: Overall survival of the study group was significantly better than that of an age- and gender-matched group obtained from life tables (p < 0.0001). The cardiac event-free survival rates at 1, 2 and 3 years were 99.2%, 97.8% and 97.4%, respectively. The cardiac event rate per person-year of follow-up was 0.9%. Subgroups with an intermediate or high pretest probability of having coronary artery disease also had low cardiac event rates. Multivariate predictors of subsequent cardiac events were angina during treadmill exercise testing (risk ratio [RR] 4.1, 95% confidence interval [CI] 1.5 to 11.0), low work load (defined as < 7 metabolic equivalents [METs] for men and < 5 METs for women; RR 3.2, 95% CI 1.4 to 7.6), echocardiographic left ventricular hypertrophy (RR 2.6, 95% CI 1.1 to 6.3) and advancing age (RR 1.04/year, 95% CI 1.0 to 1.1)., Conclusions: The outcome after normal exercise echocardiography is excellent. Subgroups with an intermediate or high pretest probability of having coronary artery disease also have a favorable prognosis after a normal exercise echocardiogram. Characteristics predictive of subsequent cardiac events (i.e., patient age, work load, angina during exercise testing and echocardiographic left ventricular hypertrophy) should be considered in the clinical interpretation of a normal exercise echocardiogram.

Objectives: This report characterizes the paradoxical sinus deceleration occasionally observed during dobutamine stress testing and determines its relation to myocardial ischemia., Background: Dobutamine stress echocardiography is widely accepted as a noninvasive tool for evaluating coronary artery disease. With infusion of dobutamine, there is typically a dose-dependent increase in heart rate. However, in some patients, a paradoxical decrease in heart rate has been observed during high dose dobutamine infusion., Methods: In 181 consecutive patients undergoing both dobutamine stress echocardiography and coronary angiography, electrocardiographic (ECG) data collected during dobutamine infusion were reviewed to identify patients with a decrease in heart rate. The clinical, stress echocardiographic, hemodynamic and angiographic correlates of patients with a decrease in heart rate were reviewed., Results: A decrease in heart rate ranging from 7 to 64 beats/min occurred during high dose dobutamine infusion in 14 patients (8%, 95% confidence interval [CI] 6% to 10%), including 3 in whom a junctional rhythm developed. The decrease was sudden in five patients (36%, 95% CI 13% to 65%) and gradual in nine (64%, 95% CI 35% to 87%). A decrease in blood pressure (12 patients [86%], 95% CI 57% to 98%) with simultaneous chest pain (7 patients [50%], 95% CI 23% to 77%) and nausea (5 patients [36%], 95% CI 13% to 65%) was common. Significant coronary artery disease (> or = 50% diameter stenosis) was present in 8 (57%) of 14 patients (95% CI 29% to 82%). Two patients (14%, 95% CI 2% to 43%) had no clinical, ECG or echocardiographic evidence of ischemia and no significant coronary artery disease by angiography. There was no increased incidence of right coronary artery stenosis in patients with paradoxical sinus deceleration., Conclusions: Paradoxical sinus deceleration occurs in 8% of patients during dobutamine stress testing. Although most often observed in patients with coronary artery disease, it can occur in the absence of ischemia and coronary artery disease, and in some patients may be due to a vasodepressor reflex.

Objectives: This study sought to evaluate the role and incremental value of atropine in a large patient group undergoing dobutamine stress echocardiography., Background: The use of atropine to potentiate dobutamine stress is not standard practice. Although the utility of atropine has been described, data on its incremental value remain limited and do not exist for a routine clinical practice setting., Methods: Dobutamine stress echocardiography was performed in 1,171 patients with use of a standard protocol. Atropine (maximal dose 2.0 mg) was given to 299 patients (26%) who did not attain target heart rate. Coronary angiography was performed in 183 patients (46 received atropine), 148 of whom were found to have significant coronary artery disease (> or = 70% diameter stenosis in a major epicardial vessel, > or = 50% stenosis for left main coronary artery disease). All tests were reviewed independently by experienced observers., Results: There were no major adverse events. Patients receiving atropine had a lower rest heart rate (65 vs. 74 beats/min, p < 0.0001) and more often received beta-adrenergic blocking agents (49% vs. 14%, p < 0.0001). Of 444 patients in whom stress-induced ischemia developed, 70 (16%) required atropine before ischemia became evident. Sensitivity for detection of significant coronary artery disease was 90% with dobutamine alone and 95% after the addition of atropine. In 66 patients with normal wall motion at rest, test sensitivity was 65% before and 84% after atropine was given. Atropine use did not compromise test specificity. New diagnostic information was obtained in 20 (50%) of 40 patients with angiographic coronary artery disease given atropine. Proportionately more patients with single-vessel disease required atropine before an ischemic response was observed; this effect appeared related to the higher ischemic threshold in these patients., Conclusions: Augmentation of heart rate had a modest influence on the overall diagnostic sensitivity of dobutamine stress echocardiography in our study cohort. However, it was particularly helpful in patients receiving beta-blockers and those with milder coronary disease. Despite the use of > or = 1 mg of atropine in some patients, this incremental value was not achieved at the expense of safety.

Objectives: This study sought to compare manifestations of myocardial ischemia evoked by exercise and dobutamine echocardiography in patients with left main coronary artery disease., Background: During exercise testing, left ventricular cavity dilation, marked ST segment depression and blood pressure decrease indicate severe coronary artery disease. Whether these signs are comparably evoked by dobutamine echocardiography has not been described., Methods: Fifty-four patients who underwent stress echocardiography (36 exercise, 18 dobutamine) and coronary angiography showing > or = 50% left main stenosis were analyzed. Electrocardiographic and blood pressure changes, symptoms, wall motion score indexes and sensitivity for coronary artery disease were compared. In 47 patients, the left ventricular endocardium was traced to quantify volumes and ejection fraction., Results: Stress-induced regional wall motion abnormalities developed in 91% of patients; this was not different on exercise (89%) or dobutamine echocardiography (94%). Rate-pressure product and wall motion score index, similar at rest, tended to be higher after exercise than after dobutamine stress (p = 0.07 and p = 0.05, respectively). ST segment depression > or = 1 mm was more common with exercise (p = 0.005). Ejection fraction and end-systolic and end-diastolic volume indexes were comparable at rest in both groups. With exercise, ejection fraction decreased in 87% of patients, and end-systolic and end-diastolic volume indexes increased in 80%. In contrast, with dobutamine, decreased ejection fraction and increased volume indexes were infrequent. Ejection fraction was lower ([mean +/- SD] 45 +/- 19% vs. 54 +/- 12%, p = 0.007) and end-diastolic (69 +/- 26 vs. 50 +/- 17 ml/m2, p =0.02) and end-systolic (39 +/- 20 vs. 24 +/- 13 ml/m2, p = 0.02) volume indexes were higher after exercise than after dobutamine stress., Conclusions: On the basis of changes in regional wall motion both dobutamine and exercise echocardiography have a comparable high sensitivity in diagnosing myocardial ischemia in left main coronary artery disease. However, conventional signs of severe myocardial ischemia, including left ventricular cavity dilation and marked ST segment depression, occur more often with exercise than with dobutamine echocardiography.

Objectives: This study examined the ability of exercise echocardiography to identify multivessel coronary artery disease and ascertain its incremental value when combined with clinical and exercise test variables., Background: Although exercise echocardiography has been shown to be accurate for the detection of coronary artery disease, little is known about its utility for identifying multivessel involvement, and its incremental value when combined with clinical and exercise test variables has not been studied., Methods: One hundred fifty consecutive patients were selected on the basis of having had an exercise echocardiographic and a coronary angiographic study within 6 months without any revascularization procedure. Significant coronary artery disease (> or = 50% diameter stenosis in any major coronary artery) was present in 117 patients, and multivessel (two- or three-vessel) disease was present in 90 patients. The exercise echocardiographic studies were reviewed by an experienced observer unaware of the results of the coronary angiogram., Results: The overall sensitivity and specificity of exercise echocardiography for the identification of multivessel disease were 73% and 70%, respectively. A stepwise logistic regression analysis identified the number of abnormal regions on the postexercise images as the strongest independent predictor of multivessel disease; also significant were a history of myocardial infarction and ST segment depression of at least 2 mm on the peak exercise electrocardiogram., Conclusions: Exercise echocardiography adds independent and incremental information to clinical and exercise test variables for identifying multivessel coronary artery disease.

The prognostic importance of coronary artery disease at the time of elective abdominal aortic aneurysmectomy was evaluated among 131 residents of Olmsted County, Minnesota who underwent elective aneurysmectomy from 1971 to 1987 and were followed up to 1988 for death and cardiac events (cardiac death, myocardial infarction, coronary bypass surgery and angioplasty). Before aneurysmectomy, 75 patients (Group 1) had no clinically recognized coronary disease, 47 patients (Group 2) had suspected or overt uncorrected coronary artery disease (history of prior myocardial infarction, angina or a positive stress test) and 9 patients (Group 3) had undergone coronary artery bypass grafting or coronary angioplasty. The 30 day operative mortality rate was 3% (2 of 75) in Group 1 and 9% (4 of 47) in Group 2 (p = 0.15). According to Kaplan-Meier analysis, estimated survival 8 years after aneurysmectomy was 59% (expected rate 68%, p = 0.29) in Group 1 versus 34% (expected rate 61%, p = 0.01) in Group 2. The cumulative incidence rate of cardiac events at 8 years was 15% and 61%, respectively, for patients without and with suspected/overt coronary artery disease (p less than 0.01). Using multivariable proportional hazards analysis, uncorrected coronary artery disease was associated with a nearly twofold increased risk of death (hazard ratio 1.79, 95% confidence interval 1.06 to 3.00) and a fourfold increased risk of cardiac events (hazard ratio 3.71, 95% confidence interval 1.79 to 7.69). These population-based data support an aggressive life-long approach to the management of coronary artery disease in patients undergoing abdominal aortic aneurysmectomy.