Bailey, Kent R.

BACKGROUND Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.

BACKGROUND Quantitation of valvular regurgitation remains a challenge. The accuracy of quantitative Doppler is controversial, and its ability to measure regurgitant volume is unknown; therefore, it is not widely used. METHODS AND RESULTS In 120 patients (20 without regurgitation, 19 with aortic regurgitation, and 81 with mitral regurgitation), the stroke volume through the mitral annulus and left ventricular outflow tract were measured using pulsed-wave Doppler concurrently with left ventricular stroke volume calculated using left ventricular volumes measured by two-dimensional echocardiography Simpson's biapical method. Regurgitant volume and fraction were thus computed using Doppler or ventricular methods. In normal patients there were good correlations between Doppler and left ventricular measurements of stroke volume. Doppler regurgitant volume and fraction were 4.4 +/- 4.4 mL and 5.3 +/- 4.5%, respectively. In patients with aortic regurgitation, there were good correlations between Doppler and left ventricular measurements of stroke volume, regurgitant volume, and regurgitant fraction (r = 0.97, r = 0.95, and r = 0.93, respectively; p < 0.0001). In patients with mitral regurgitation, despite good correlations between Doppler and ventricular methods for stroke volume, regurgitant volume, and regurgitant fraction (r = 0.94, r = 0.93, and r = 0.94, respectively; p < 0.001), these variables were overestimated by Doppler. However, in the last 54 patients compared with the first 27, overestimation decreased significantly for regurgitant volume (5 +/- 10 mL versus 18 +/- 27 mL, p < 0.05) and regurgitant fraction (3.3 +/- 6.7% versus 6.2 +/- 6.8%, p = 0.05). CONCLUSIONS Quantitative Doppler can be performed in large numbers of patients in a clinical laboratory. Its potential limitation was identified as overestimation of mitral regurgitation, which is overcome with increased experience. Its achieved accuracy in mitral and aortic regurgitation allows measurement not only of regurgitant fraction but most importantly of regurgitant volume.

BACKGROUND The implications of hypotension occurring during dobutamine stress echocardiography have not been elucidated. We observed in some patients that hyperdynamic left ventricular function developed during dobutamine stress echocardiography and hypothesized that intracavitary obstruction was occurring and might account for hypotension in some patients. METHODS AND RESULTS Fifty-seven consecutive patients undergoing dobutamine stress echocardiography underwent pulsed-wave and continuous-wave Doppler examination of the left ventricular cavity at rest and at peak dobutamine infusion. The development of an intraventricular gradient with dobutamine stress was defined as a late-peaking left ventricular Doppler velocity profile that exceeded basal velocity by at least 1 m/sec. During dobutamine stress testing, left ventricular outflow velocity or intracavitary velocity increased in all patients. Obstruction occurred in 12 patients (21%, group 1). Group 2 was the remaining 45 patients. Peak velocities in group 1 ranged from 2.0 to 5.0 m/sec (mean, 3.5 m/sec), and the mean increase from velocity at rest was 2.3 m/sec. The mean change in systolic blood pressure was significantly lower in patients in group 1 (-15 versus 4 mm Hg, p = 0.02). When the 18 patients with an ischemic response to stress testing (evidenced by new or worsening wall motion abnormalities) were excluded from analysis, systolic blood pressure response was still significantly different for the two groups (-19 versus 2 mm Hg, p = 0.03). CONCLUSIONS Dynamic left ventricular obstruction is a new observation; it may develop frequently in patients undergoing dobutamine stress echocardiography. Obstruction rather than ischemia may explain a decrease in blood pressure during dobutamine stress echocardiography.

To identify genes influencing blood pressure response to an angiotensin II receptor blocker, single nucleotide polymorphisms identified by genome-wide association analysis of the response to candesartan were validated by opposite direction associations with the response to a thiazide diuretic, hydrochlorothiazide. We sampled 198 white and 193 blacks with primary hypertension from opposite tertiles of the race-sex–specific distributions of age-adjusted diastolic blood pressure response to candesartan. There were 285 polymorphisms associated with the response to candesartan at P <10 −4 in whites. A total of 273 of the 285 polymorphisms, which were available for analysis in a separate sample of 196 whites, validated for opposite direction associations with the response to hydrochlorothiazide (Fisher χ 2 1-sided P =0.02). Among the 273 polymorphisms, those in the chromosome 11q21 region were the most significantly associated with response to candesartan in whites (eg, rs11020821 near FUT4 , P =8.98×10 −7 ), had the strongest opposite direction associations with response to hydrochlorothiazide (eg, rs3758785 in GPR83 , P =7.10×10 −3 ), and had the same direction associations with response to candesartan in the 193 blacks (eg, rs16924603 near FUT4 , P =1.52×10 −2 ). Also notable among the 273 polymorphisms was rs11649420 on chromosome 16 in the amiloride-sensitive sodium channel subunit SCNN1G involved in mediating renal sodium reabsorption and maintaining blood pressure when the renin-angiotensin system is inhibited by candesartan. These results support the use of genomewide association analyses to identify novel genes predictive of opposite direction associations with blood pressure responses to inhibitors of the renin-angiotensin and renal sodium transport systems.

AbstractBACKGROUNDSoluble intercellular adhesion molecule 1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration.METHODSsICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification (CAC) through year 20 (n = 2378), and both carotid artery stenosis (n = 2432) and intima-media thickness (IMT) at year 20 (n = 2240).RESULTSMedian sICAM-1 was 145.9 μg/L. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% CI 0.003–0.017 mm) higher per SD of sICAM-1 (44 μg/L) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol-lowering medication. With the same adjustment, the odds ratio (OR) for the presence of year-20 carotid artery stenosis per SD of sICAM-1 was 1.12 (95% CI 1.01–1.25, P &lt; 0.04), whereas for occurrence of CAC progression the OR was 1.16 (1.04–1.31, P &lt; 0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution.CONCLUSIONSsICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades before the development of clinical CVD.

We hypothesized that higher serum levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) are associated with lower functional capacity in patients with peripheral arterial disease ([PAD] n = 481, mean age 67, 68% men). Functional capacity was quantified as distance walked on a treadmill for 5 minutes. Patients were divided into 3 groups according to the distance walked: >144 yards (group 1, n = 254); 60 to 144 yards (group 2, n = 80); <60 yards or did not walk (group 3, n = 147). The association between NT-pro-BNP levels and the ordinal 3-level walking distance was assessed using multivariable ordinal logistic regression analyses that adjusted for several possible confounding variables. Higher levels of NT-pro-BNP were associated with a lower ordinal walking category independent of possible confounders (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.28-1.77; P < .001). In conclusion, higher levels of NT-pro-BNP are independently associated with lower functional capacity in patients with PAD and may be a marker of hemodynamic stress in these patients.

Abstract To test recommended anticoagulation measures as predictors of 180-day venous thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents with incident VTE over the 14-year period of 1984-1997, and followed each case (N = 1166) forward in time for VTE recurrence. We tested the activated partial thromboplastin time (APTT), international normalized ratio (INR), and other measures of heparin and warfarin anticoagulation as predictors of VTE recurrence while controlling for baseline and time-dependent characteristics using Cox proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients received heparin and warfarin, respectively, and 85 (8%) developed VTE recurrence. In multivariable analyses, increasing proportions of time on heparin with an APTT ≥ 0.2 anti-Xa U/mL and on warfarin with an INR ≥ 2.0 were associated with significant reductions in VTE recurrence, while the hazard with active cancer was significantly increased. Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement were not independent predictors of recurrence. At a heparin dose ≥ 30 000 U/d, the median proportion of time with an APTT ≥ 0.2 anti-Xa U/mL was 92%, suggesting that routine APTT monitoring and heparin dose adjustment may be unnecessary. In summary, lower-intensity heparin and standard-intensity warfarin anticoagulation are effective in preventing VTE recurrence.

We investigated the burden of frailty across the spectrum of ankle-brachial index (ABI < 0.9, 0.9 ≤ ABI < 1.1, 1.1 ≤ ABI < 1.4 and ≥1.4) using data from the National Health and Nutritional Examination Survey (NHANES) in respondents aged >50 years. Criteria used to identify frailty status included weight loss, slow walking speed, weakness, exhaustion, and low physical activity. Participants meeting 1 to 2 criteria were classified as prefrail, and those meeting ≥3 criteria were classified as frail. Prevalence of frailty in respondents with ABI < 0.9 (17.5%) and 0.9 ≤ ABI < 1.1 (6.7%) was higher than in participants with normal ABI-1.1 ≤ ABI < 1.4 (4.7%). In multivariable multinomial logistic regression models, ABI < 0.9 predicted frailty (odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.08-4.94) and prefrailty (OR = 1.36, 95% CI = 0.90-2.07). Higher prevalence of frailty was seen in participants with ABI ≥ 1.4 (7.3%), P = .39. Frailty predicted general and cardiovascular mortality in participants with ABI < 0.9. Frailty mediates increased morbidity and mortality seen in peripheral arterial disease (PAD).

To improve the predictive accuracy of the signal-averaged electrocardiogram, we created a linear logistic model for predicting ventricular tachycardia during electrophysiologic testing. This signal-averaged electrocardiographic model was created from data obtained from 214 patients undergoing electrophysiologic testing (70 had ventricular tachycardia during electrophysiologic testing) by using stepwise logistic regression to rank eight clinical and nine signal-averaged electrocardiographic variables. The best predictors were ejection fraction, history of infarction, ventricular ectopic pairs or nonsustained ventricular tachycardia on Holter monitoring, QRS duration after 25-Hz filtering, and root mean square voltage of the terminal 40 msec of the QRS complex after 40- and 80-Hz filtering. Cross validation (a statistical technique that can be used to accurately evaluate how a predictive model will perform on a prospective patient population) was used to validate the model. After cross validation, the model's sensitivity was 91% and specificity was 59% for predicting ventricular tachycardia during electrophysiologic testing. This model compared favorably with established 25-Hz late-potential criteria (QRS duration of more than 110 msec and root mean square voltage of less than 25 microV of the terminal 40 msec of the QRS complex; sensitivity, 64%; specificity, 85%) and with established 40-Hz late-potential criteria (QRS duration of more than 114 msec or root mean square voltage of less than 20 microV of the terminal 40 msec of the QRS complex or duration of the low-amplitude signal less than 40 microV at the terminal QRS complex that is greater than 38 msec; sensitivity, 84%; specificity, 54%).(ABSTRACT TRUNCATED AT 250 WORDS)

Studies correlating prosthetic valve gradients determined by continuous wave Doppler echocardiography with gradients obtained by cardiac catheterization have, to date, been limited to patients with mitral and tricuspid prostheses or have compared nonsimultaneous measurements. Simultaneous Doppler and catheter pressure gradients in 36 patients (mean age, 63 +/- 13 years) with 42 prosthetic valves (20 aortic, 20 mitral, one tricuspid, and one pulmonary) were studied. Catheter gradients were obtained using a dual-catheter technique. The simultaneous pressure tracings and Doppler flow velocity profiles were digitized at 10-msec intervals to derive the corresponding maximal and mean gradients. The correlation between the maximal Doppler gradient and the simultaneously measured maximal catheter gradient was 0.94 (SEE = 6), and that between the Doppler gradient and the simultaneously measured mean catheter gradient was 0.96 (SEE = 3). There were no significant differences in correlation between gradients for the 32 mechanical valves (maximal gradients: r = 0.95, SEE = 6; mean gradients: r = 0.96, SEE = 3) and the 10 bioprosthetic valves (maximal gradients: r = 0.89, SEE = 6; mean gradients: r = 0.93, SEE = 3). In patients with mitral prostheses, Doppler gradients correlated well with the corresponding catheter gradients obtained with direct measurement of left atrial pressure (maximal gradients: r = 0.96, SEE = 2; mean gradients: r = 0.97, SEE = 1.2). A close correlation between corresponding Doppler and catheter gradients also was found in patients with aortic prostheses (maximal gradients: r = 0.94, SEE = 6; mean gradients: r = 0.94, SEE = 3). Thus, continuous wave Doppler echocardiography can accurately predict the pressure gradient across prosthetic valves.