Biomedical subjects

Douglas W Mahoney

Publications and source records attributed to Douglas W Mahoney.

At least 19 recordsLinked to original sources

PubMed2006

Joint estimation of calibration and expression for high-density oligonucleotide arrays.

MOTIVATION: The need for normalization in microarray experiments has been well documented in the literature. Currently, many analysis methods treat normalization and analysis as a series of steps, with summarized data carried forward to the next step. RESULTS: We present a unified algorithm which incorporates normalization and class comparison in one analysis using probe level perfect match and mismatch data. The algorithm is based on calibration models common to most biological assays, and the resulting chip-specific parameters have a natural interpretation. We show that the algorithm fits into the statistical generalized linear models framework, describe a practical fitting strategy and present results of the algorithm applied to an example dataset as well as based on metrics used in affycomp. The algorithm ranks amongst the top third of the affycomp competitors, performing best in measures of bias. AVAILABILITY: R functions are available on request from the authors.

Algorithms↗

PubMed2006

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide: biomarkers for mortality in a large community-based cohort free of heart failure.

Recent studies report that, in the absence of heart failure and renal failure, plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We sought to confirm and extend these previous studies to assess BNP, measured by 3 distinct assays, as a biomarker for mortality in a strategy to enhance efforts at primary prevention and to better understand the clinical phenotype of such subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted County, Minn, and individuals with heart or renal failure were excluded. BNP was assessed using 3 assays including Biosite and Shionogi for mature, biologically active BNP and the Roche assay for apparently nonbiologically active amino-terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were recorded for all of the participants. Median follow-up for mortality was 5.6 years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and Biosite assays remained significant even after adjustment for traditional clinical risk factors and echocardiographic abnormalities including left ventricular hypertrophy and diastolic dysfunction. Echocardiography documented widespread structural changes in those with increasing BNP levels yet below levels observed in heart failure. We report in a large, well-characterized community-based cohort, free of heart failure, the first study to compare 3 distinct BNP assays as biomarkers for mortality in the same cohort. Our findings confirm the potential use of NT-proBNP and BNP biomarkers for future events and underscore that these peptides may also serve as biomarkers for underlying cardiac remodeling secondary to diverse cardiovascular disease entities.

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PubMed2006

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.

OBJECTIVES: This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample. BACKGROUND: Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample. METHODS: Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age > or =45 years) of Olmsted County, Minnesota. RESULTS: In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction < or =40% or < or =50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone. CONCLUSIONS: Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.

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PubMed2006

Prevalence of syncope in a population aged more than 45 years.

PURPOSE: Our current understanding of the prevalence of syncope is based on a few small studies of highly selected populations. We sought to estimate the prevalence and recurrence rate of syncope in the general population aged more than 45 years and to analyze their associations with age and sex. METHODS: We performed a cross-sectional survey of 1925 randomly selected residents of Olmsted County, Minn, 45 years or older, from January 1998 to August 2000. RESULTS: The median age of the 1925 participants was 62 years, and 905 (47.0%) were male. Overall, 364 subjects reported an episode of syncope in their lifetime, giving an estimated prevalence of 19% (95% confidence interval, 17%-21%). The age-specific prevalence rates were 45 to 54 years (20%), 55 to 64 years (20%), 65 to 74 years (15%), and 75 years or more (21%) (P = .86). Females reported a higher prevalence of syncope (22% vs 15%, P < .001). CONCLUSIONS: The prevalence of syncope is estimated at 19% in the general population aged more than 45 years. Females have a higher prevalence, and there is no association of syncope prevalence with age.

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PubMed2005

Echocardiographic characteristics of electrocardiographically unrecognized myocardial infarctions in a community population.

Unrecognized myocardial infarction (UMI) as diagnosed by surveillance electrocardiography has been shown to carry the same poor prognosis as recognized myocardial infarction (RMI). The echocardiographic characteristics of UMI have never been studied before. Due to a similar prognosis, we hypothesized that UMI and RMI would exhibit similar degrees of echocardiographic ventricular dysfunction. We studied a random community cohort of 2,042 adults who were > or =45 years of age in a cross-sectional setting in Olmsted County, Minnesota. RMI was diagnosed by review of medical records and UMI was diagnosed if the electrocardiogram met MI criteria without a previous MI recorded in the medical record. All subjects underwent transthoracic echocardiography. We identified 80 patients who had UMI and 101 who had RMI. In bivariate analyses, a stepwise increase in echocardiographic abnormalities was observed from participants who had no MI to UMI to RMI: respective mean ejection fractions were 63%, 61%, and 55; prevalences in left ventricular enlargement were 13%, 22%, and 52%; mean left ventricular mass indexes were 98, 103, and 118 g/m(2); prevalences in regional wall motion abnormality were 2%, 13%, and 42%; and prevalences in diastolic dysfunction were 25%, 56%, and 65% (p for trend <0.0001 for all comparisons). After adjusting for standard coronary risk factors, patients who had UMI continued to exhibit significant abnormalities in systolic dysfunction, diastolic dysfunction, and regional wall motion abnormality, although to a lesser extent than patients who had RMI. In conclusion, patients who have UMI manifest structural abnormalities more commonly than do patients who have no MI but less commonly than do those who have RMI. The similar prognosis after UMI and RMI cannot be explained by comparable degrees of ventricular damage.

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PubMed2005

Relation of QRS duration on the surface 12-lead electrocardiogram with mortality in patients with known or suspected coronary artery disease.

The aim of this study was to assess the relation between QRS duration and mortality in patients with known or suspected coronary artery disease, after adjustment for myocardial functional abnormalities, as assessed by exercise echocardiography. We studied 4,033 patients (age 62 +/- 12 years; 2,360 men, 18% with previous myocardial infarction) who underwent symptom-limited exercise echocardiography. The QRS duration was electronically measured from the 12-lead electrocardiogram. The incremental value of the QRS duration for predicting mortality was assessed by adding the QRS duration at the end of each of these modeling steps: clinical data, exercise electrocardiographic, and exercise echocardiographic variables. The QRS duration correlated positively with age, the wall motion score index at rest, and percentage of ischemic segments and negatively with workload (p = 0.0001). Of the 4,033 patients, 252 died during a median follow-up of 3 years. The QRS duration was univariately associated with an increased risk of death (relative risk 8.5, 95% confidence interval CI 4.4 to 16.4, p <0.0001). In an incremental multivariate model, the clinical predictors of mortality were age, male gender, previous infarction, and diabetes mellitus (chi-square 122). Workload was incremental to clinical data in the exercise test model (chi-square 193, p <0.0001). The exercise wall motion score index was incremental to both models (chi-square 211, p <0.001). The QRS duration was associated with an incremental risk of death when added to the clinical model (chi-square 133, p = 0.009), exercise test model (chi-square = 203, p = 0.002), and echocardiographic model (chi-square = 216, p = 0.03). A QRS duration > or =105 ms best identified patients at increased risk. In conclusion, QRS duration is associated with an increased risk of death, even after adjustment for clinical factors, exercise capacity, left ventricular function, and exercise-induced myocardial ischemia.

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PubMed2005

Diastolic dysfunction and left atrial volume: a population-based study.

OBJECTIVES: We examined the association between diastolic function and left atrial volume indexed to body surface area (LAVi) in a population-based study. BACKGROUND: Atrial enlargement has been suggested as a marker of the severity and duration of diastolic dysfunction (DD). However, the association between DD and atrial enlargement and their individual prognostic implications in the population is poorly defined. METHODS: A cross-sectional sample of Olmsted County, Minnesota, residents > or =45 years of age (n=2,042) underwent comprehensive Doppler echocardiography and medical record review. RESULTS: The LAVi increased with worsening DD: 23 +/- 6 ml/m2 (normal), 25 +/- 8 ml/m2 (grade I DD), 31 +/- 8 ml/m2 (grade II DD), 48 +/- 12 ml/m2 (grades III to IV DD). In bivariate analyses, age, left ventricular mass index, and DD grade were positively associated, whereas female gender and ejection fraction (EF) were inversely associated with LAVi (p <0.001 for all). When controlling for age, gender, cardiovascular (CV) disease, EF, and left ventricular mass, grade II DD was associated with a 24%, and grade III to IV DD was associated with a 62% larger LA volume (p <0.0001 for both). The area under the receiver-operator characteristic curve for LAVi to detect grade I, grade II, or grade III to IV DD was 0.57, 0.81, and 0.98, respectively. Both DD and LAVi were predictive of all-cause mortality, but when controlling for DD, LAVi was not an independent predictor of mortality. CONCLUSIONS: These data suggest that DD contributes to LA remodeling. Indeed, DD is a stronger predictor of mortality; presumably it better reflects the impact of CV disease within the general population.

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PubMed2005

Prognosis of patients with good exercise capacity and mildly abnormal exercise echocardiography results: identification of an at-risk subgroup.

BACKGROUND: Patients with good exercise capacity and mildly abnormal exercise echocardiography results have a favorable overall prognosis. OBJECTIVE: We sought to define subgroups that might be at higher risk. METHODS: We examined outcomes of 868 patients (women, > or = 5 metabolic equivalents; men, > or = 7 metabolic equivalents) with mild rest- or exercise-induced wall-motion abnormalities and evaluated potential predictors of time to cardiac death or nonfatal myocardial infarction (MI). RESULTS: Mean age was 64 +/- 10 years; 477 patients (55%) were men. Mean follow-up was 3.1 +/- 1.5 years; cardiac event rate was 1.2% per person-year. A history of MI was the only significant predictor (risk ratio, 3.9; 95% confidence interval, 1.9-7.8; P = .0001), with 1-, 3-, and 5-year event-free survival of 98.5% +/- 1.1%, 92.6% +/- 2.6%, and 83.3% +/- 5.1%, respectively (event rate, 3.4%). CONCLUSIONS: Patients with a history of MI have a higher annual cardiac event rate and may benefit from reevaluation, whereas no history of MI connotes a favorable prognosis.

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PubMed2005

Inhibition evaluation for a 20-min endotoxin limit test on FDG.

OBJECTIVES: In chemical quality control tests for 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG), gel time is inversely related to endotoxin concentration. Solutions for positive product control (PPC) and positive water control (PWC) should contain a highly concentrated endotoxin level. The aims of our study were to derive an endotoxin concentration that causes PPC and PWC to gel and to evaluate inhibitory effects caused by FDG on gel formation in PPC and PWC test solutions. METHODS: At expiration, the maximum administered total dose (in millilitres) of FDG should contain fewer than 175 endotoxin units (EU). Our average batch volume of FDG is 15 ml; thus, the minimum endotoxin limit should be 12 EU x ml(-1) . Twelve tubes were tested for each of four concentrations. Inhibition was assessed using Limulus amoebocyte lysate reagent, depyrogenated vials, and pyrogen-free sterile micropipette tips. Each study was performed with four groups of solutions: decayed 18F-FDG, negative control, PPC and PWC. RESULTS: In the study of undiluted FDG, seven of 50 PPC vials at 12 EU x ml(-1) did not gel. The lowest endotoxin concentration that consistently gelled at 20 min was 4 EU x ml(-1) . In the sample tested for inhibition using PPC tubes at 4 EU x ml(-1) , 49 tubes gelled at 20 min, and one did not. CONCLUSION: The inhibition rate improved between undiluted (i.e., 7/50 (14%)) and diluted (i.e., 1/50 (2%)) FDG PPC trials (P=0.03). However, given that 1 of 50 trials failed for diluted FDG PPC, we conclude that inhibition still occurs and there is a 95% chance that the inhibition rate could be as high as 11% or as low as 0% on repetition of the experiment.

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PubMed2005

Identification of optimal electrocardiographic criteria for the diagnosis of unrecognized myocardial infarction: a population-based study.

BACKGROUND: Despite using the same tool (ECG), the proportion of myocardial infarctions that goes unrecognized varies from 20% to 60% in population-based studies. The reasons for such wide variations have not been studied. We sought to evaluate the effect of ECG-MI criteria and study methodology on the prevalence of unrecognized myocardial infarction (UMI) and to identify the optimal ECG-MI criteria for UMI detection in epidemiologic studies. METHODS: A random population-based sample of 2042 adults, age > or = 45 years, underwent history, medical record abstraction and ECG. Six different ECG-MI criteria and two subjective recognized myocardial infarction (RMI) identification criteria, from different published studies, were applied to the same survey ECG. The operating test characteristics of different criteria were compared with the objective criterion standard of a RMI by Gillum criteria. RESULTS: The UMI proportion estimates varied from 32% to 61% due to variation in ECG-MI criteria, while keeping the study population, MI recognition criteria, and ECG constant. Subjective criteria for MI recognition had limited value (positive predictive value of 44-93%) in picking up RMI. Depending on the ECG abnormality used to define MI, ECG reading had widely varying sensitivity (21-37%; P < 0.0001) with consistently high specificity (92-97%) for detection of RMI. CONCLUSIONS: The prevalence estimates of UMI vary widely and are strongly dependent on the ECG-MI and MI recognition criteria. Future studies of UMI should explicitly recognize this variation and select the ECG-MI criteria that match their study aims.

Cross-Sectional Studies↗

PubMed2004

Prognostic value of exercise echocardiography in patients with classic angina pectoris.

The role of stress echocardiography in the prognostic evaluation of patients with angina pectoris is not well defined. This study included 437 patients (241 men and 196 women) with angina pectoris and a pretest probability of coronary artery disease (CAD) of > or = 0.7 who were referred for exercise echocardiography. No patient had a history of acute myocardial infarction or coronary revascularization. Mean age was 65 +/- 10 years. During a median follow-up of 2.7 years, hard cardiac events (cardiac death or nonfatal myocardial infarction) occurred in 19 patients and 53 patients underwent coronary revascularization. Event-free survival rates in patients with normal versus abnormal stress echocardiograms were 98% versus 83% at 1 year, 96% versus 75% at 3 years, and 87% versus 69% at 5 years, respectively. In a multivariate analysis of clinical, exercise stress, and echocardiographic parameters, independent predictors of hard cardiac events were Q waves on the electrocardiogram (chi-square 8.7, p = 0.003) and the presence of wall motion abnormalities during exercise in multivessel distribution (chi-square 5.3, p = 0.02). In an incremental model of clinical, exercise, and echocardiographic variables for the prediction of all cardiac events, the addition of echocardiographic data increased the chi-square of the model from 62 to 78 (p = 0.0003). Exercise echocardiography provides useful information in the risk stratification of patients with suspected CAD and a high pretest probability of CAD. Patients with normal exercise echocardiograms have a low event rate and therefore can be exempted from invasive procedures during the 3 years after a normal exercise echocardiogram.

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PubMed2004

Plasma brain natriuretic peptide to detect preclinical ventricular systolic or diastolic dysfunction: a community-based study.

BACKGROUND: Preclinical systolic or diastolic dysfunction is associated with increased morbidity and mortality. We postulated that plasma brain natriuretic peptide (BNP) might serve as a biomarker for preclinical ventricular dysfunction (PCVD) but that the discriminatory values for BNP may vary with age and sex. METHODS AND RESULTS: We measured BNP, systolic and diastolic ventricular function, and clinical parameters in 2042 randomly selected residents of Olmsted County, Minn, aged 45 years or older. For preclinical systolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with more severe (0.82 to 0.92) than any (0.51 to 0.74) systolic dysfunction and were similar in men and women and in younger and older persons. For preclinical diastolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with moderate-to-severe (0.74 to 0.79) than any (0.52 to 0.68) diastolic dysfunction and were similar regardless of age or sex. Optimal discriminatory values of BNP varied with age and sex. Considering the prevalence of preclinical systolic or diastolic dysfunction and the predictive characteristics observed, using BNP to screen for PCVD would necessitate echo in 10% to 40% of those screened, with most confirmatory echocardiograms being negative, and would miss 10% to 60% of those affected. CONCLUSIONS: BNP is a suboptimal screening test for PCVD in the population.

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PubMed2004

Use of a scoring model combining clinical, exercise test, and echocardiographic data to predict mortality in patients with known or suspected coronary artery disease.

The aim of this study was to derive and validate a model for predicting mortality by combining clinical, exercise testing, and echocardiographic data in patients with known or suspected coronary artery disease. We studied 5,679 patients (aged 62 +/- 12 years; 3,231 men) who were followed for a mean of 3 years after treadmill exercise echocardiography. Patients were randomly divided into 2 groups of equal size. (1) The modeling group underwent multivariate analysis to define independent predictors of mortality. Three hundred bootstrap resamplings were performed to determine parameter coefficients. Patients were divided into 5 risk categories according to their composite score and survival rate in each category was estimated by the Kaplan-Meier method. (2) The validation group comprised patients for whom the risk model was applied. Patients were divided into 5 risk categories based on data obtained from the modeling group. During follow-up, 315 patients died (151 in the modeling group). Independent predictors of mortality were exercise wall motion score index (chi-square 22.4, p <0.0001), workload (chi-square 17.1, p <0.0001), male gender (chi-square 15.4, p <0.0001), and age (chi-square 5.5, RR 1.02, 95% confidence interval 1 to 1.04; p = 0.02). Application of the composite score in the validation group resulted in an effective stratification of patients for mortality and cardiac events. This study provides a model for assessing risk of death by combining clinical, exercise testing, and echocardiographic data using a single composite score.

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PubMed2004

Akinesia becoming dyskinesia after exercise testing: prevalence and relationship to clinical outcome.

OBJECTIVES: The aim of this study was to determine the prevalence and prognostic implications of dyskinesia developing after exercise. BACKGROUND: The prevalence and prognostic implications of new-onset dyskinesia with exercise testing have not been previously described. METHODS: We considered 1005 consecutive patients who underwent exercise echocardiography and had akinetic segments at rest. Patients were divided according to the presence or absence of exercise-induced dyskinesia. Baseline clinical and echocardiographic parameters were compared, and patients were followed up for a median of 2.7 years. RESULTS: One hundred four (10%) patients developed dyskinesia after exercise. Compared to patients with segments that remained akinetic, these patients were more likely to have electrocardiographic (ECG) evidence of prior myocardial infarction and, during exercise, had a less pronounced rise in systolic blood pressure and more often had ECG evidence of ischemia. Their resting left ventricular (LV) ejection fraction was worse and improved little after exercise. However, all-cause mortality and the incidence of major adverse cardiac events were similar in the two groups, even after correction for age, gender, and resting LV function (hazard ratio for major adverse cardiac events = 1.36, 95% confidence interval [CI] 0.82 to 2.26, p = 0.23; hazard ratio for total mortality = 1.20, 95% CI 0.75 to 1.94, p = 0.45). CONCLUSIONS: One in 10 patients with akinetic myocardium at rest will develop dyskinesia after exercise. This is associated with poorer LV function at rest and little improvement in systolic function after exercise. However, this response has no impact on prognosis.

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PubMed2004

Participation bias in a population-based echocardiography study.

PURPOSE: To compare the characteristics of participants and non-participants in a population-based study of cardiac ventricular function. METHODS: Subjects aged 45 years and older on January 1, 1997 were recruited from a sampling frame of Olmsted County residents from the Rochester Epidemiology Project. Subjects were asked to complete a 17-page questionnaire and participate in a 4-hour clinical examination that included a brief physical examination, echocardiography, spirometry, and an electrocardiogram. With specific IRB approval, the community medical records of participants and non-participants from the first wave of recruitment were examined by trained nurse abstractors to elicit details of past medical history. RESULTS: Of the first 963 persons invited to participate in the study, 488 (51%) completed all phases of the examination. Participation rates were similar among men and women (53% vs. 49%, respectively). By age, participation rates were lowest among persons aged 75 years and older (44.7% and 34.9%) and 45 to 54 years (45.4% and 44.3%) for men and women. Participation rates were not different according to past history of coronary heart disease, congestive heart failure, or other cardiovascular disease. Persons with a history of chronic obstructive pulmonary disease were less likely to participate (19.4% vs. 51%; odds ratio, 0.36; 95% confidence interval, 0.18, 0.76) after adjustment for age, sex, and comorbid conditions. CONCLUSIONS: These results provide some reassurance that participation bias in this study may have little influence on its overall findings, although this cannot be conclusive.

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PubMed2004

Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure.

OBJECTIVES: Questionnaires are used to estimate disease burden. Agreement between questionnaire responses and a criterion standard is important for optimal disease prevalence estimates. We measured the agreement between self-reported disease and medical record diagnosis of disease. STUDY DESIGN AND SETTING: A total of 2,037 Olmsted County, Minnesota residents > or =45 years of age were randomly selected. Questionnaires asked if subjects had ever had heart failure, diabetes, hypertension, myocardial infarction (MI), or stroke. Medical records were abstracted. RESULTS: Self-report of disease showed >90% specificity for all these diseases, but sensitivity was low for heart failure (69%) and diabetes (66%). Agreement between self-report and medical record was substantial (kappa 0.71-0.80) for diabetes, hypertension, MI, and stroke but not for heart failure (kappa 0.46). Factors associated with high total agreement by multivariate analysis were age <65 years, female sex, education >12 years, and zero Charlson Index score (P < .05). CONCLUSION: Questionnaire data are of greatest value in life-threatening, acute-onset diseases (e.g., MI and stroke) and chronic disorders requiring ongoing management (e.g.,diabetes and hypertension). They are more accurate in young women and better-educated subjects.

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PubMed2004

Outcomes of patients with reduced exercise capacity at time of exercise echocardiography.

OBJECTIVE: To characterize the prognostic implications of exercise echocardiography in patients who have reduced exercise capacity at the time of testing. PATIENTS AND METHODS: We examined the outcomes of 941 patients at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and December 31, 1995, who had reduced exercise capacity on exercise echocardiography (women, <5 metabolic equivalents; men, <7 metabolic equivalents) and evaluated the potential association between clinical, electrocardiographic, and echocardiographic variables and outcomes for patients with normal vs abnormal exercise echocardiograms. We used variables of independent prognostic value to estimate cardiac risk. RESULTS: For patients with normal exercise echocardiograms (n=282), the rate of cardiac death or nonfatal myocardial infarction was 09% per person-year of follow-up, and previous coronary revascularization was the only predictor of the time to cardiac event. For patients with abnormal exercise echocardiograms (n=659), the cardiac event rate was 4.4%. Independent predictors of outcome were exercise left ventricular (LV) ejection fraction (risk ratio, 1.44 per 10% decrement; 95% confidence interval, 1.2-1.7; P<.001) and an increase or no change in LV end-systolic size in response to exercise (risk ratio, 2.22; 95% confidence interval, 1.2-4.1; P=.01). CONCLUSION: Exercise echocardiographic findings have important prognostic implications for patients who have reduced exercise capacity on testing. Echocardiographic descriptors of LV systolic function and dysfunction obtained immediately after exercise can be used to stratify cardiac risk of patients who do not achieve a level of exercise ordinarily considered to be of "diagnostic" value.

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PubMed2003

Prognostic significance of impairment of heart rate response to exercise: impact of left ventricular function and myocardial ischemia.

OBJECTIVES: The goal of this research was to study the association between heart rate (HR) response to exercise and the risk of death and myocardial infarction (MI) after adjustment for left ventricular (LV) function and myocardial ischemia. BACKGROUND: Chronotropic incompetence during exercise testing is associated with increased mortality. It is unknown whether LV dysfunction or ischemia accounts for this. METHODS: We studied 3,221 patients (age 59 +/- 12 years; 1,701 men) who underwent treadmill exercise echocardiography. We considered two markers of chronotropic incompetence: 1) failure to achieve 85% of the maximal predicted HR, and 2) low (<0.8) chronotropic index. The independent association between HR response and end points was evaluated by an adjusted risk (AR) model, which included clinical parameters, ejection fraction, and the severity of ischemic wall motion abnormalities. RESULTS: Target HR was not achieved in 495 (15%) patients. Low chronotropic index was observed in 793 (25%) patients. There were 129 deaths (41 cardiac) during a median follow-up of 3.2 years. Myocardial infarction occurred in 65 patients. Low chronotropic index was associated with cardiac death (AR, 1.54; 95% confidence interval [CI], 1.18 to 2.04; p = 0.002) and MI (AR, 1.37; 95% CI, 1.09 to 1.69; p = 0.007). Failure to achieve 85% of maximal predicted HR was associated with increased mortality (AR, 1.49; 95% CI, 1.02 to 2.22; p = 0.04) and cardiac death (AR, 2.13; 95% CI, 1.10 to 4.17; p = 0.03). CONCLUSIONS: Impaired chronotropic response to exercise is associated with increased mortality and cardiac events even after adjusting for LV function and the severity of exercise-induced myocardial ischemia.

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