Introduced house sparrows (Passer domesticus) have greater variation in DNA methylation than native house sparrows.

As a highly successful introduced species, house sparrows (Passer domesticus) respond rapidly to their new habitats, generating phenotypic patterns across their introduced range that resemble variation in native regions. Epigenetic mechanisms likely facilitate the success of introduced house sparrows by aiding particular individuals to adjust their phenotypes plastically to novel conditions. Our objective here was to investigate patterns of DNA methylation among populations of house sparrows at a broad geographic scale that included different introduction histories: invading, established, and native. We defined the invading category as the locations with introductions less than 70 years ago and the established category as the locations with greater than 70 years since introduction. We screened DNA methylation among individuals (n = 45) by epiRADseq, expecting that variation in DNA methylation among individuals from invading populations would be higher when compared with individuals from established and native populations. Invading house sparrows had the highest variance in DNA methylation of all three groups, but established house sparrows also had higher variance than native ones. The highest number of differently methylated regions were detected between invading and native populations of house sparrow. Additionally, DNA methylation was negatively correlated to time-since introduction, which further suggests that DNA methylation had a role in the successful colonization's of house sparrows.

Epigenetic potential: Promoter CpG content positively covaries with lifespan and is dependent on gene function among vertebrates.

Variation in DNA methylation is associated with many ecological and life history traits, including niche breadth and lifespan. In vertebrates, DNA methylation occurs almost exclusively at "CpG" dinucleotides. Yet, how variation in the CpG content of the genome impacts organismal ecology has been largely overlooked. Here, we explore associations between promoter CpG content, lifespan and niche breadth among 60, amniote vertebrate species. The CpG content of 16 functionally relevant gene promoters was strongly, positively associated with lifespan in mammals and reptiles, but was not related to niche breadth. Possibly, by providing more substrate for CpG methylation to occur, high promoter CpG content extends the time taken for deleterious, age-related errors in CpG methylation patterns to accumulate, thereby extending lifespan. The association between CpG content and lifespan was driven by gene promoters with intermediate CpG enrichment-those known to be predisposed to regulation by methylation. Our findings provide novel support for the idea that high CpG content has been selected for in long-lived species to preserve the capacity for gene expression regulation by CpG methylation. Intriguingly, promoter CpG content was also dependent on gene function in our study; immune genes had on average 20% less CpG sites than metabolic- and stress-related genes.

Association of percentile ranking with citation impact and productivity in a large cohort of de novo NIMH-funded R01 grants.

Previous reports from National Institutes of Health and National Science Foundation have suggested that peer review scores of funded grants bear no association with grant citation impact and productivity. This lack of association, if true, may be particularly concerning during times of increasing competition for increasingly limited funds. We analyzed the citation impact and productivity for 1755 de novo investigator-initiated R01 grants funded for at least 2 years by National Institute of Mental Health between 2000 and 2009. Consistent with previous reports, we found no association between grant percentile ranking and subsequent productivity and citation impact, even after accounting for subject categories, years of publication, duration and amounts of funding, as well as a number of investigator-specific measures. Prior investigator funding and academic productivity were moderately strong predictors of grant citation impact.

NO synthase-positive striatal interneurons are decreased in schizophrenia.

The gaseous messenger NO has repeatedly been suggested to play a role in the pathogenesis of psychoses. Following a pilot study, we investigated whether the number of nitrinergic neurons in the putamen of patients suffering from schizophrenia, bipolar disorder or major depression is altered. Post-mortem striatum sections of 15 brains from patients with either disease were examined by NADPH-diaphorase staining, which selectively labels NO synthase-positive interneurons. Quantification of these cells revealed significantly lower numbers of NO synthase-containing neurons in the putamen of schizophrenic patients. Our results suggest that striatal nitrinergic interneurons are involved in the pathophysiology of at least some forms of schizophrenia, such as e.g. catatonic schizophrenia.

Heart rate recovery immediately after treadmill exercise and left ventricular systolic dysfunction as predictors of mortality: the case of stress echocardiography.

BACKGROUND: An attenuated heart rate recovery after exercise has been shown to be predictive of mortality. In prior studies, recovery heart rates were measured while patients were exercising lightly, that is, during a cool-down period. It is not known whether heart rate recovery predicts mortality when measured in the absence of a cool-down period or after accounting for left ventricular systolic function. METHODS AND RESULTS: We followed 5438 consecutive patients without a history of heart failure or valvular disease referred for exercise echocardiography for 3 years. Heart rate recovery was defined as the difference in heart rate between peak exercise and 1 minute later; a value

Blood pressure response during treadmill testing as a risk factor for new-onset hypertension. The Framingham heart study.

BACKGROUND: Although systolic blood pressure (SBP) response to exercise has been shown to predict subsequent hypertension in small samples of men, this association has not been studied in a large population-based sample of middle-aged men and women. The purpose of this study was to examine, in normotensive subjects, the relations of SBP and diastolic blood pressure (DBP) during the exercise and recovery periods of a graded treadmill test to the risk of developing new-onset hypertension. METHODS AND RESULTS: BP data from exercise testing in 1026 men and 1284 women (mean age, 42+/-10 years; range, 20 to 69 years) from the Framingham Offspring Study who were normotensive at baseline were related to the incidence of hypertension 8 years later. New-onset hypertension, defined as an SBP >/=140 mm Hg or DBP >/=90 mm Hg or the initiation of antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%). Exaggerated SBP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of SBP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than the 95th percentile during the second stage of exercise and third minute of recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05) and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in men in a multivariable model that included exercise duration and peak exercise BP (OR, 1.92; CI, 1.00, 3.69). Baseline resting SBP (chi2, 23.4 in men and 34.7 in women) and DBP (chi2, 11.3 in men and 13.1 in women) had stronger associations with new-onset hypertension than exercise DBP (chi2, 16.4 in men and 6.1 in women) and recovery SBP (chi2, 6.5 in men and 2.1 in women) responses. CONCLUSIONS: An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. An elevated recovery SBP was predictive of hypertension in men. These findings may reflect subtle pathophysiological features in the preclinical stage of hypertension.

Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention.

BACKGROUND: Established methods of risk assessment in percutaneous coronary intervention have focused on clinical and anatomical lesion characteristics. Emerging evidence indicates the substantial contribution of inflammatory processes to short-term and long-term outcomes in coronary artery disease. METHODS AND RESULTS: Within a single-center registry of contemporary percutaneous coronary revascularization strategies with postprocedural creatine kinase and clinical events routinely recorded, we assessed the association of baseline C-reactive protein with death or myocardial infarction within the first 30 days. Predictive usefulness of baseline C-reactive protein within the context of established clinical and angiographic predictors of risk was also examined. Among 727 consecutive patients, elevated baseline C-reactive protein before percutaneous coronary intervention was associated with progressive increase in death or myocardial infarction at 30 days (lowest quartile, 3.9%, versus highest quartile, 14.2%; P=0.002). Among clinical and procedural characteristics, baseline C-reactive protein remained independently predictive of adverse events, with the highest quartile of C-reactive protein associated with an odds ratio for excess 30-day death or myocardial infarction of 3.68 (95% CI, 1.51 to 8.99; P=0.004). A predictive model that included baseline C-reactive protein quartiles, American College of Cardiology/American Heart Association lesion score, acute coronary syndrome presentation, and coronary stenting appears strongly predictive of 30-day death or myocardial infarction within this population (C-statistic, 0.735) and among individual patients (Brier score, 0.006). CONCLUSIONS: Elevated baseline C-reactive protein portends heightened risk of 30-day death or myocardial infarction after coronary intervention. Coupled anatomic, clinical, and inflammatory risk stratification demonstrates strong predictive utility among patients undergoing percutaneous coronary intervention and may be useful for guiding future strategies.

Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the progression of calcific aortic stenosis.

BACKGROUND: Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis. METHODS AND RESULTS: A retrospective study of 174 patients (mean age 68+/-12 years) with mild to moderate calcific aortic stenosis was conducted. Patients required normal left ventricular function, /=2 echocardiograms performed at least 12 months apart. Fifty-seven patients (33%) received treatment with a statin; the remaining 117 (67%) did not. The statin group was older and had a higher prevalence of hypertension, diabetes mellitus, and coronary disease. During a mean follow-up of 21 months, patients treated with statin had a smaller increase in peak and mean gradient and a smaller decrease in aortic valve area. When annualized, the decrease in aortic valve area for the nonstatin group was 0.11+/-0.18 cm(2) compared with 0.06+/-0.16 cm(2) for those treated with a statin (P=0.03). In multivariate analysis, statin usage was a significant independent predictor of a smaller decrease in valve area (P=0.01) and a lesser increase in peak gradient (P=0.02). CONCLUSIONS: Statin-treated patients, despite a higher risk profile for progression, had reduced aortic stenosis progression compared with those not treated with a statin. These data provide justification for a prospective randomized trial to substantiate whether statin therapy slows the progression of aortic stenosis.

Ventilatory and heart rate responses to exercise : better predictors of heart failure mortality than peak oxygen consumption.

BACKGROUND: An abnormally low chronotropic response and an abnormally high ventilatory response (V(E)/V(CO2)) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. METHODS AND RESULTS: Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V(O2) and V(E)/V(CO2) were directly measured. Chronotropic index and peak V(O2) were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V(E)/V(CO2) was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V(E)/V(CO2) low chronotropic index, low V(O2), low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V(E)/V(CO2) and peak V(O2), it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V(E)/V(CO2) (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). CONCLUSIONS: The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.

Attenuation of rebound ischemia after discontinuation of heparin therapy by glycoprotein IIb/IIIa inhibition with eptifibatide in patients with acute coronary syndromes: observations from the platelet IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

Background- A reactivation of ischemia after the discontinuation of intravenous heparin in acute coronary syndromes has been described. The effect of glycoprotein IIb/IIIa blockade on heparin rebound is unknown. Methods and Results- Patients with acute coronary syndromes who received heparin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial were analyzed. Rates of death or myocardial (re)infarction while on heparin therapy and in 12-hour periods in the 2 days after heparin discontinuation were compared between eptifibatide and placebo. There was no difference between study groups in event rates during heparin infusion. In the 12 hours after heparin discontinuation, there was a 2.5-fold increase in all events, an 8-fold increase in death, and a 2-fold increase in myocardial infarction. However, in the 12 hours after heparin discontinuation, there was a significantly lower rate of events (1.68% versus 2.53%, P=0.03) and death (0.77% versus 0.21%, P=0.002) in the eptifibatide group compared with the placebo group. When only considering patients who were on study drug at the time of heparin discontinuation, the reduction in the combined end point was marginally significant, but the difference in the rate of death remained significant (0.68% versus 0.06%, P=0.004). In logistic regression analyses, the multivariate predictors of rebound events were the duration of heparin therapy, age, North American site, and lack of eptifibatide treatment. Conclusions- An increase in death or myocardial infarction occurs in the 12 hours after heparin discontinuation in patients with acute coronary syndromes. This rebound is attenuated by glycoprotein IIb/IIIa inhibition with eptifibatide.

Influence of contemporary versus 30-year blood pressure levels on left ventricular mass and geometry: the Framingham Heart Study.

To determine whether long-term blood pressure levels correlate with left ventricular mass, echocardiographic measurements were performed in 152 men and 299 women who were participants in the Framingham Heart Study. All subjects were free of obesity and cardiovascular and pulmonary disease, were not taking antihypertensive medications and had echocardiographic studies that were adequate for estimating left ventricular mass. Thirty-year average systolic blood pressure was correlated with left ventricular mass (corrected for height) (r = 0.27, p less than 0.001 in men; r = 0.31, p less than 0.001 in women). Multivariate linear regression analyses taking into account age and body mass index showed 30-year average systolic blood pressure to be a significant independent predictor of left ventricular mass (p less than 0.01 in men and women). Systolic blood pressure at echocardiography was not independently associated with left ventricular mass when 30-year systolic blood pressure was entered into the multivariate model. The prevalence of left ventricular hypertrophy was associated with 30-year average systolic blood pressure (odds ratio for every 20-mm Hg increase in blood pressure: 3.20, p less than 0.05 in men; 3.27, p less than 0.001 in women). The increase in left ventricular mass associated with 30-year average systolic blood pressure reflected changes in left ventricular wall thickness but not in left ventricular internal dimension. Thirty-year average diastolic blood pressure was also correlated with left ventricular mass but to a lesser degree than was systolic blood pressure (r = 0.18, p less than 0.05 in men; r = 0.18, p less than 0.01 in women).(ABSTRACT TRUNCATED AT 250 WORDS)

Separate and joint influences of obesity and mild hypertension on left ventricular mass and geometry: the Framingham Heart Study.

Increased left ventricular mass has been shown to be a significant independent predictor of cardiovascular risk. The purpose of this study was to assess the separate and combined relations of obesity and hypertension with left ventricular mass and geometry. Echocardiographic findings in subjects in the Framingham Heart Study who were free of cardiopulmonary disease and were not taking cardiovascular medications were examined. M-mode studies that were adequate for estimating left ventricular mass were available in 624 men and 1,209 women. Height and weight measured at the time of echocardiography were used to calculate body mass index (in kg/m2), a measure of obesity. Casual sitting blood pressure measurements were obtained to detect rest hypertension. In subgroup analyses of lean normotensive, obese normotensive, lean hypertensive and obese hypertensive subjects, hypertension and obesity each had significant independent associations with left ventricular mass and wall thickness (all p less than 0.001 in men and women). Obesity was also associated with left ventricular internal diameter (p less than 0.001 in men and women). There were no synergistic influences of hypertension and obesity on any echocardiographic left ventricular variables. It is concluded that obesity and hypertension each have distinct associations with left ventricular mass and geometry. These strengths of association are additive but not synergistic.

Gender-specific reference M-mode values in adults: population-derived values with consideration of the impact of height.

OBJECTIVES: The purpose of this investigation was to derive population-based reference values for M-mode echocardiographic dimensions that can be applied in epidemiologic studies, clinical trials and clinical practice and to determine optimal methods for adjusting these dimensions for body size. BACKGROUND: M-mode echocardiography remains an important modality for studying cardiovascular disease; this is especially true with regard to detecting target organ damage in systemic hypertension. Most previously published reference values were derived from hospital-based series or relatively small samples and were not gender specific. METHODS: Using a sample of 288 men and 524 women who were between 20 and 45 years of age and who were free of cardiovascular disease, reference values were derived for end-diastolic and end-systolic left ventricular internal dimensions, left ventricular wall thickness and left atrial dimension. The relations between these dimensions and height, a measure of body size relatively independent of obesity, were investigated using various regression models. RESULTS: Nomograms for mean and 95th percentile values in men and women were constructed on the basis of linear regression models relating echocardiographic dimensions to height. Adjustment for body surface area greatly attenuated associations between obesity and cardiac dimensions in a separate healthy but less restricted sample of 411 men and 503 women. CONCLUSIONS: Gender-specific M-mode reference values and nomograms, with mean and 95th percentile values for echocardiographic dimensions as a function of height, are reported. The use of body surface area as means of body size adjustment is called into question.

Delayed systolic blood pressure recovery after graded exercise: an independent correlate of angiographic coronary disease.

OBJECTIVE: This study was performed to determine whether a delayed decline in systolic blood pressure (SBP) after graded exercise is an independent correlate of angiographic coronary disease. BACKGROUND: The predictive importance of the rate of SBP decline after exercise relative to blood pressure changes during exercise has not been well explored. METHODS: Among adults who underwent symptom-limited exercise treadmill testing and who underwent coronary angiography within 90 days, a delayed decline in SBP during recovery was defined as a ratio of SBPs at 3 min of recovery to SBP at 1 min of recovery >1.0. Severe angiographic coronary artery disease was defined as left main disease, three-vessel disease or two-vessel disease with involvement of the proximal left anterior descending artery. RESULTS: There were 493 subjects eligible for analyses (age 59 +/- 11 years, 78% male). Severe angiographic coronary disease was noted in 102 (21%). There were associations noted between a delayed decline in SBP during recovery and severe angiographic coronary disease (34% vs. 17%, odds ratio [OR] 2.59, confidence interval [CI] 1.58 to 4.25, p = 0.001). In multivariate logistic regression analyses adjusting for SBP changes during exercise and other potential confounders, a delayed decline in SBP during recovery remained predictive of severe angiographic coronary disease (adjusted OR 2.22, 95% CI 1.27 to 3.87, p = 0.005). CONCLUSIONS: A delayed decline in SBP during recovery is associated with a greater likelihood of severe angiographic coronary disease even after accounting for the change in SBP during exercise.

Use of exercise echocardiography for prognostic evaluation of patients with known or suspected coronary artery disease.

OBJECTIVES: This study prospectively compared the incremental prognostic benefit of exercise echocardiography with that of exercise testing in a large cohort. BACKGROUND: Exercise echocardiography is widely accepted as a diagnostic tool, but the prognostic information provided by this test, incremental to clinical and stress testing evaluation, is ill-defined. METHODS: Clinical, exercise and echocardiographic variables were studied in a consecutive group of 500 patients undergoing exercise echocardiography. After exclusion of patients who underwent revascularization within 3 months of the stress test (n = 16, 3%) and those lost to follow-up (n = 21, 4%), the remaining 463 patients (mean [+/-SD] age 57 +/- 12 years, 302 men) were followed-up for 44 +/- 11 months. Outcome was related to the exercise and echocardiographic findings, and the incremental prognostic benefit of exercise echocardiography was compared with that of standard exercise testing. RESULTS: Cardiac events occurred in 81 patients (17%), including 33 (7%) with spontaneous events (cardiac death, myocardial infarction and unstable angina) and 48 with late revascularizations due to progressive symptoms. In a multivariate Cox proportional hazards model, the likelihood of any cardiac event was increased in the presence of ischemia (relative risk [RR] 5.06, 95% confidence interval [CI] 3.09 to 8.29, p < 0.001) and lessened by more maximal stress, measured as percent age-predicted maximal heart rate (RR per 5% increment 0.84, 95% CI 0.77 to 0.92, p < 0.001). Spontaneous events were more strongly predicted by ischemia (RR 8.20, 95% CI 3.41 to 19.71, p < 0.001) and percent age-predicted maximal heart rate (RR per 5% increment 0.78, 95% CI 0.67 to 0.91, p < 0.001). An interactive logistic regression model showed that the addition of echocardiographic to exercise and clinical data offered incremental predictive value. CONCLUSIONS: The presence of ischemia on the exercise echocardiogram can predict whether patients will experience an event. This relation is independent of, and incremental to, clinical and exercise data.

Prediction of mortality using dobutamine echocardiography.

OBJECTIVES: We sought to find out whether dobutamine echocardiography (DbE) could provide independent prediction of total and cardiac mortality, incremental to clinical and angiographic variables. BACKGROUND: Existing outcome studies with DbE have examined composite end points, rather than death, over a relatively short follow-up. Clinical and stress data were collected in 3,156 patients (age 63 +/- 12 years, 1,801 men) undergoing DbE. Significant stenoses (>50% diameter) were identified in 70% of 1,073 patients undergoing coronary angiography. Total and cardiac mortality were identified over nine years of follow-up (mean 3.8 +/- 1.9). Cox models were used to analyze the effect of ischemia and other variables, independent of other determinants of mortality. RESULTS: The dobutamine echocardiogram was abnormal in 1,575 patients (50%). Death occurred in 716 patients (23%), 259 of whom (8%) were thought to have died from cardiac causes. Patients with normal DbE had a total mortality of 8% per year and a cardiac mortality of 1% per year over the first four years of follow-up. Ischemia and the extent of abnormal wall motion were independent predictors of cardiac death, together with age and heart failure. In sequential Cox models, the predictive power of clinical data alone (model chi-square 115) was strengthened by adding the resting left ventricular function (model chi-square 138) and the results of DbE (model chi-square 181). In the subgroup undergoing coronary angiography, the power of the model was increased to a minor degree by the addition of coronary anatomy data. CONCLUSIONS: Dobutamine echocardiography is an independent predictor of death, incremental to other data. While a normal dobutamine echocardiogram predicts low risk of cardiac death (on the order of 1% per year), this risk increases with the extent of abnormal wall motion at rest and stress.

Independent contribution of myocardial perfusion defects to exercise capacity and heart rate recovery for prediction of all-cause mortality in patients with known or suspected coronary heart disease.

OBJECTIVES: The goal of this study was to determine the value of thallium201 single photon emission computed tomography (SPECT) imaging for prediction of all-cause mortality when considered along with functional capacity and heart rate recovery. BACKGROUND: Myocardial perfusion defects identified by thallium201 SPECT imaging are predictive of cardiac events. Functional capacity and heart rate recovery are exercise measures that also have prognostic implications. METHODS: We followed 7,163 consecutive adults referred for symptom-limited exercise thallium SPECT (mean age 60 +/- 10, 25% women) for 6.7 years. Using information theory, we identified a probable best model relating nuclear findings to outcome to calculate a prognostic nuclear score. RESULTS: There were 855 deaths. Intermediate- and high-risk prognostic nuclear scores were noted in 28% and 10% of patients. Compared with those with low-risk scans, patients with an intermediate-risk score were at increased risk for death (14% vs. 9%, hazard ratio: 1.67, 95% confidence interval [CI]: 1.44 to 1.95, p < 0.0001), while those with high-risk scores were at greater risk (24%, hazard ratio: 2.98, 95% CI: 2.49 to 3.56, p < 0.0001). In multivariable analyses that adjusted for clinical characteristics, functional capacity and heart rate recovery, an intermediate-risk nuclear score remained predictive of death (adjusted hazard ratio: 1.50, 95% CI: 1.28 to 1.76, p < 0.0001), as did a high-risk score (adjusted hazard ratio: 2.76, 95% CI: 2.13 to 2.56, p < 0.0001). Impaired functional capacity and decreased heart rate recovery provided additional prognostic information. CONCLUSIONS: Myocardial perfusion defects detected by thallium SPECT imaging are independently predictive of long-term all-cause death, even after accounting for exercise capacity, heart rate recovery and other potential confounders.

Demonstration of a posterior atrial input to the atrioventricular node during sustained anterograde slow pathway conduction.

OBJECTIVES: This study sought to demonstrate electrophysiologic evidence for the existence of different anatomic atrial input sites of fast and slow conduction pathways in patients with dual atrioventricular (AV) node physiology. BACKGROUND: Although a separate posterior exit site exists for a retrograde slow AV node pathway, it remains unresolved whether a separate atrial input site into the AV node actually exists in patients with dual anterograde AV node pathway physiology. METHODS: In 10 patients with dual AV node pathway physiology, atrial pacing at three chosen drive cycle lengths (DCL1, DCL2 and DCL3) was performed at an anterior site (A) just above the His bundle recording site and at a posterior atrial site (P) just below the coronary sinus ostium. DCL3 was chosen as the one cycle length that resulted in a long AH interval consistent with slow pathway conduction. The stimulus to His bundle conduction times (SH) at both sites (SH(P) and SH(A), respectively) and their differences (deltaSH = SH(P) - SH(A)) at each of the three drive cycle lengths were analyzed. RESULTS: The mean +/- SD deltaSH values for DCL1 and DCL2 measured 9 +/- 16 and 8 +/- 18 ms, respectively, and the mean deltaSH value at DCL3 measured -34 +/- 24 ms, which was significantly different from the mean deltaSH values at DCL1 and DCL2 (both p < 0.05). CONCLUSIONS: The significant change in the deltaSH (SH(P) - SH(A)) value during slow pathway conduction could be accounted for by a corresponding shift of anterograde input from an anterior to a posterior entry site to the AV node. These findings support the notion that a separate anterograde entry site of the slow pathway does exist in patients with dual AV node pathway physiology.

Angiographic and prognostic implications of an exaggerated exercise systolic blood pressure response and rest systolic blood pressure in adults undergoing evaluation for suspected coronary artery disease.

OBJECTIVES: This study was designed to assess the angiographic and prognostic implications of an exaggerated systolic blood pressure response to exercise ("exercise hypertension") in adults undergoing evaluation for suspected coronary artery disease. BACKGROUND: The clinical implications of exercise hypertension are unclear. METHODS: Subjects for this prospective cohort study were derived from a consecutive sample of 9,608 adults who were referred for treadmill testing and who augmented their systolic blood pressure by at least 10 mm Hg. There were 594 subjects who underwent coronary angiography within 90 days of treadmill testing. Exercise hypertension was defined as a peak exercise systolic blood pressure > or = 210 mm Hg in men and > or = 190 mm Hg in women. Severe angiographic coronary disease was defined as left main coronary artery disease (> or = 50% diameter stenosis), three-vessel disease (> or = 70% diameter stenosis) or two-vessel disease with > or = 70% diameter stenosis of the proximal left anterior descending coronary artery. All-cause mortality was assessed during a follow-up period of approximately 2 years. RESULTS: Exercise hypertension was present in 196 subjects (33%). Severe coronary disease was less common in subjects with exercise hypertension (14% vs. 25%, odds ratio 0.51, 95% confidence interval [CI] 0.32 to 0.81, p = 0.004). Exercise hypertension remained associated with a lower rate of severe coronary disease even after adjusting for rest hypertension, age, gender, exercise capacity and other possible confounders. During the follow-up period, there were 23 deaths; only 2 occurred in the group with exercise hypertension. After adjusting for severity of coronary disease, exercise hypertension remained associated with a lower mortality rate (adjusted relative risk 0.20, 95% CI 0.05 to 0.84, p = 0.03). CONCLUSIONS: In adults evaluated for coronary artery disease, exercise hypertension is associated with a lower likelihood of angiographically severe disease and a lower adjusted mortality rate.