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Biomedical subjects

J S Borer

Publications and source records attributed to J S Borer.

At least 19 recordsLinked to original sources
PubMed2000

Severe mitral regurgitation due to mitral valve prolapse: risk factors for development, progression, and need for mitral valve surgery.

Patients with mitral valve prolapse (MVP) may develop severe mitral regurgitation (MR) and require valve surgery. Preliminary data suggest that high body weight and blood pressure might add to the irreversible factors of older age and male gender in increasing risk of these complications. Fifty-four patients with severe MR due to MVP were compared with 117 control subjects with uncomplicated MVP to elucidate factors independently associated with severe MR: the need for valve surgery and the cumulative risk of requiring mitral valve surgery. Patients with severe MR were older (p<0.00005), more overweight (p = 0.002), had higher systolic (p = 0.0003) and diastolic (p = 0.007) blood pressures, and were more likely to have hypertension (p = 0.0001) and to be men (p<0.001). In both groups, men had higher blood pressure and relative body weight than women. In multivariate analysis, older age was most strongly associated with MR; higher body mass index, hypertension, and gender were independent predictors of severe MR in analyses that excluded age. Among the 54 patients with severe MR, the 32 (59%) who underwent mitral valve surgery during 11 years of follow-up were older, more overweight, and more likely to be hypertensive than those not requiring surgery. Among patients undergoing mitral valve surgery in 3 centers, mitral prolapse was the etiology in 25%, 67% of whom were men. Using these data and national statistics, we estimate that the gender-specific cumulative risk for requiring valvular surgery for severe MR in subjects with MVP is 0.8% in women and 2.6% in men before age 65, and 1.4% and 5.5% by age 75. Thus, subjects with MVP who are older, more overweight, and hypertensive are at greater risk for severe MR and valve surgery. Higher blood pressure and relative weight in men with MVP appear to contribute to the gender difference in risk for severe MR.

Adolescent↗
PubMed2000

Abnormal gene expression of cardiac fibroblasts in experimental aortic regurgitation.

Extensive primary fibrosis precedes heart failure and death in experimental chronic aortic regurgitation. To seek the molecular basis for this observation, this study analyzed the RNA pool for genes that are up-or downregulated in aortic regurgitation fibroblasts. Differential display reverse transcriptase polymerase chain reaction was used to compare RNA extracted from cardiac fibroblasts isolated from three healthy New Zealand white rabbits and from three with aortic regurgitation. Using two base anchoring oligo d(T) primers (T11VN) together with arbitrary upstream primers, numerous differences in normal versus aortic regurgitation gene expression were apparent on differential display reverse transcriptase polymerase chain reaction. The aortic regurgitation cell cultures showed numerous differentially up-and downregulated genes compared with cell cultures of normal cardiac fibroblasts. The results showed that pathologic fibrosis in chronic experimental aortic regurgitation is associated with abnormal cardiac fibroblast gene expression, which may be pathogenic for the fibrous lesion.

Animals↗
PubMed2000

Preoperative predictors of late postoperative outcome among patients with nonischemic mitral regurgitation with 'high risk' descriptors and comparison with unoperated patients.

Among patients with chronic nonischemic mitral regurgitation (MR), high short-term mortality risk can be identified by left (LV) and/or right ventricular (RV) ejection fraction (EF) criteria (LVEF </=45% and/or RVEF </=30%). Mitral valve replacement or repair (MVR) significantly improves outcome in this subgroup, but predictors of late postoperative survival are not known, and the benefit of MVR has not been defined in patients matched for severity of LV and RV dysfunction. Therefore, prospective assessment of 14 consecutive high risk MR patients was performed before MVR and during 9 years (average) postoperatively to define echocardiographic and radionuclide angiographic predictors of survival; survival also was evaluated in a contemporaneous series of 9 high risk unoperated MR patients, and in subgroups of operated and unoperated patients matched for EF. Of 14 MVR patients, 4 died (3 cardiac: 1 sudden, 2 congestive heart failure). Only preoperative RVEF </=20% significantly predicted postoperative deaths (rest p = 0.032; exercise p = 0.05). Of 9 unoperated patients, 8 died. Mortality risk of unoperated patients remained higher than that of MVR patients when groups were matched for preoperative LVEF (p = 0.0001). Among patients with RVEF >20%, MVR significantly improved survival versus medical treatment (rest: p < 0.0001, exercise: p = 0.0003). In high risk MR patients, MVR improves survival; preoperative RV performance can define subgroups with different long-term postoperative survival.

Chronic Disease↗
PubMed1999

Prognostication in 3-vessel coronary artery disease based on left ventricular ejection fraction during exercise : influence of coronary artery bypass grafting.

BACKGROUND: Previous data indicate that left ventricular ejection fraction (LVEF) provides prognostic information among patients with coronary artery disease (CAD), but the value of such testing specifically for defining benefits of coronary artery bypass grafting (CABG) may relate to severity of exercise-inducible ischemia measured noninvasively before surgery. METHODS AND RESULTS: To determine the independent prognostic importance of preoperative ischemia severity for predicting outcomes of CABG among patients with extensive CAD, we monitored 167 stable patients with angiographically documented 3-vessel CAD (average follow-up of 9 years in event-free patients) who previously had undergone rest and exercise radionuclide cineangiography. Their course was correlated with data obtained during initial radionuclide testing, coronary arteriography, and clinical evaluation at study entry. Fifty-two patients received medical treatment only, and 115 underwent CABG (44 early [</=1 month after initial study]). Multivariate Cox model analysis indicated that change (Delta) in LVEF from rest to exercise during radionuclide study was the strongest independent predictor of major cardiac events (P=0.003) before surgery and also predicted magnitude of CABG benefit (P=0.04). Patients with DeltaLVEF -8% or less derived significant survival-prolonging and event-reducing benefit from CABG performed </=1 month after initial testing (P<0.02 for cardiac death and P=0.008 for cardiac events], early CABG versus medical-treatment-only patients); similar benefits were absent among patients with DeltaLVEF more than -8%, and among those in whom CABG was deferred. CONCLUSIONS: Assessment of ischemia severity based on LVEF response to exercise enables effective prognostication among patients with 3-vessel CAD and defines the likelihood of life-prolonging and event-reducing benefits from CABG.

Aged↗
PubMed1998

Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance.

BACKGROUND: Optimal criteria for valve replacement are unclear in asymptomatic/minimally symptomatic patients with aortic regurgitation (AR) and normal left ventricular (LV) performance at rest. Moreover, previous studies have not assessed the prognostic capacity of load-adjusted LV performance ("contractility") variables, which may be fundamentally related to clinical state. Therefore, 18 years ago, we set out to test prospectively the hypothesis that objective noninvasive measures of LV size and performance and, specifically, of load-adjusted variables, assessed at rest and during exercise (ex), could predict the development of currently accepted indications for operation for AR. METHODS AND RESULTS: Clinical variables and measures of LV size, performance, and end-systolic wall stress (ESS) were assessed annually in 104 patients by radionuclide cineangiography at rest and maximal ex and by echocardiography at rest; ESS was derived during ex. During an average 7.3-year follow-up among patients who had not been operated on, 39 of 104 patients either died suddenly (n = 4) or developed operable symptoms only (n = 22) or subnormal LV performance with or without symptoms (n = 13) (progression rate=6.2%/y). By multivariate Cox model analysis, change (delta) in LV ejection fraction (EF) from rest to ex, normalized for deltaESS from rest to ex (deltaLVEF-deltaESS index), was the strongest predictor of progression to any end point or to sudden cardiac death alone. Unadjusted deltaLVEF was almost as efficient. Symptom status modified prediction on the basis of the deltaLVEF-deltaESS index. The population tercile at highest risk by deltaLVEF-deltaESS progressed to end points at a rate of 13.3%/y, and the lowest-risk tercile progressed at 1.8%/y. CONCLUSIONS: Currently accepted symptom and LV performance indications for valve replacement, as well as sudden cardiac death, can be predicted in asymptomatic/minimally symptomatic patients with AR by load-adjusted deltaLVEF-deltaESS index, which includes data obtained during exercise.

Aortic Valve Insufficiency↗
PubMed1998

Myocardial collagen in cardiac hypertrophy resulting from chronic aortic regurgitation.

Myocardial fibrosis and abnormal myocardial collagen content are common in many forms of pathological cardiac hypertrophy, including that mediated by pressure overload. Recently, in an experimental animal model of chronic aortic regurgitation (AR), we found a strong relation between myocardial fibrosis and congestive heart failure development. To determine if these fibrotic lesions are composed of collagen, as they are in pressure overload, and to determine if potential preventive therapies should be developed similarly in both diseases, we assessed left ventricular collagen content at three time points after AR induction. Moderate to severe AR was induced in 19 New Zealand White rabbits by inserting a catheter through the carotid artery to perforate the aortic valve leaflets. Animals were killed (1) when they showed echocardiographically discernible systolic dysfunction or (2) if normal cardiac function continued, either early (1 month) or late (>3 years) after operation. Fourteen age-matched, sham-operated controls and seven normal unoperated rabbits also were studied. Collagen concentrations were determined biochemically by hydroxyproline measurement. Fibrosis was measured histologically using Mason's trichrome stain and the fibrous collagen-specific stain, Picro-Sirius Red. Our results show an age-related increase in left ventricular collagen concentration with no specific increase among animals with evidence of fibrosis. We conclude that, unlike pressure overload, volume overload produces fibrotic lesions not composed predominantly of excess collagen and that the therapy needed to prevent fibrosis may be different in these conditions. Further study is needed to define the chemical characteristics of the fibrous lesions and the pathophysiological importance of this finding.

Age Factors↗
PubMed1998

Differential response to vesnarinone by cardiac fibroblasts isolated from normal and aortic regurgitant hearts.

Vesnarinone, a quinoline derivative with modest positive inotropic action, has been shown in several studies to benefit patients with clinical congestive heart failure. The cellular basis of its clinical benefit is not known, although the drug has several pharmacologic effects demonstrated both in isolated cardiac myocytes and in other noncardiac cell types. To investigate the possibility that the clinical benefit of vesnarinone is based, at least in part, on the inhibition of pathologic myocardial fibrosis, we examined its effects on cultured cardiac fibroblasts isolated from both normal and aortic regurgitant New Zealand White rabbit hearts. As in people, rabbits with moderate-to-severe aortic regurgitation often develop congestive heart failure that, at necropsy, is characterized by exuberant myocardial fibrosis. A dose-response curve was constructed with vesnarinone concentrations ranging from 10(-4 ) to 10(-9 ) mol/L. Cellular survival was decreased by exposure to nanomolar concentrations of drug but not at the higher doses tested. Fibroblasts isolated from normal hearts responded maximally at 10(-7 ) mol/L vesnarinone, whereas fibroblasts from aortic regurgitant hearts responded maximally at 10(-8 ) mol/L. These concentrations of drug are more than an order of magnitude lower than those believed to be associated with clinical benefit from earlier studies. Our results indicate that vesnarinone can suppress cardiac fibroblast proliferation and suggest that this action may be useful in therapies designed to prevent congestive heart failure in aortic regurgitation.

Animals↗
PubMed1998

Fibrosis, myocyte degeneration and heart failure in chronic experimental aortic regurgitation.

Myocardial fibrosis and myocyte degeneration have been reported in patients with chronic aortic regurgitation (AR), and may be related to the pathophysiology of congestive heart failure (CHF) in this disease. To define the relationship between myocardial histopathologic variations and CHF in chronic AR, we performed gross and microscopic evaluations of postmortem tissue from a rabbit model of chronic AR manifesting left ventricular (LV) responses to AR similar to those in humans. Moderate-to-severe chronic AR (echocardiographic regurgitant fraction = 52 +/- 13%) was induced by closed-chest aortic valve perforation in 11 New Zealand White rabbits; 5 control rabbits were sham operated. Six of the 11 AR rabbits died 1.5 +/- 0.8 years (range 0.6-2.8 years) after AR induction; all 6 had gross and histologic anatomic evidence of CHF at necropsy. The remaining 5 AR rabbits survived until sacrifice at 2.9 +/- 0.1 years of AR; none had pathologic evidence of CHF. Cardiac hypertrophy and the extent of LV fibrosis and myocyte necrosis all were greatest among the 6 AR CHF rabbits. No inflammatory response was apparent in any animal. Moderate-to-severe chronic experimental AR frequently results in CHF which is strongly associated with myocardial fibrosis and necrosis, without evidence of inflammation. These histopathologic variations may be pathophysiologically related to CHF development.

Animals↗
PubMed1998

Time-voltage QRS area of the 12-lead electrocardiogram: detection of left ventricular hypertrophy.

Identification of left ventricular hypertrophy (LVH) using 12-lead ECG criteria based primarily on QRS amplitudes has been limited by poor sensitivity at acceptable levels of specificity. Because the product of QRS voltage and duration, as an approximation of the time-voltage area of the QRS complex, can improve accuracy of the 12-lead ECG for LVH, we examined the diagnostic value of true time-voltage area measurements of QRS complexes from the standard 12-lead ECG. Standard 12-lead ECGs and echocardiograms were obtained in 175 control subjects without LVH and in 74 patients with regurgitant valvular heart disease and LVH defined by echocardiographic criteria (indexed LV mass >110 g/m2 in women and >125 g/m2 in men). Standard voltage criteria, voltage-duration products (voltage multiplied by QRS duration), and true time-voltage areas of the QRS were calculated for Sokolow-Lyon criteria (SV1 +RV(5/6)) and the 12-lead sum of voltage criteria. Test sensitivities were compared using gender-specific partitions with matched specificity of 98% in the 175 subjects without LVH. Measurement of the time-voltage area significantly improved sensitivity for both criteria. The 76% sensitivity of the 12-lead sum area and 65% sensitivity of Sokolow-Lyon area were significantly greater than the 54% sensitivity of the approximation of QRS area provided by each voltage-duration product (P<.001 and P=.021) and than the 46% and 43% sensitivities of the respective simple voltage criteria (each P<.001). Comparison of receiver operating characteristic curves confirmed the superior overall performance of time-voltage area criteria compared with both voltage-duration products and simple voltage criteria. These results suggest that use of time-voltage areas can dramatically improve identification of LVH by 12-lead ECG. Further study of this approach is needed to identify optimal criteria for LVH based on the time-voltage area measurements from the 12-lead ECG.

Echocardiography↗
PubMed1997

Relation of ultra-low frequency heart rate variability to the clinical course of chronic aortic regurgitation.

We examined the relation of the standard deviation of the 5-minute mean RR intervals over 24 hours (SDANN), a measure of ultra-low frequency heart rate variability (HRV) (<0.0033 Hz), and other measures of HRV to clinical outcome events in 50 asymptomatic or minimally symptomatic patients with chronic severe aortic regurgitation (AR) who underwent ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular diseases. At entry, all patients were in sinus rhythm and had New York Heart Association functional class I or minimal II congestive heart failure, with left ventricular (LV) ejection fraction > or = 45% and LV end-diastolic dimension > or = 5.5 cm in women and > or = 5.9 cm in men. End points were defined as progression to aortic valve replacement (n = 19) or sudden cardiac death (n = 1) during the mean follow-up period of 8.1 +/- 3.8 years. With the median SDANN of 145 ms as a partition value, the average annual risk of end-point events in patients with low SDANN was significantly greater than the event rate in patients with high SDANN (11%/year vs 2%/year, p <0.0003). In multivariate analysis, reduced SDANN was associated with end-point events independent of LV function, LV end-systolic dimension, and symptom status (p = 0.001). We conclude that reduced ultra-low frequency HRV measured as SDANN is strongly related to progression to valve surgery in asymptomatic and minimally symptomatic patients with chronic AR.

Adult↗
PubMed1997

Usefulness of subnormal midwall fractional shortening in predicting left ventricular exercise dysfunction in asymptomatic patients with systemic hypertension.

We have recently shown that a subgroup of asymptomatic hypertensive patients exhibit subnormal left ventricular (LV) midwall fiber shortening at rest and that this finding predicts morbidity and mortality independently of age, blood pressure (BP), or the presence of LV hypertrophy. However, it is unknown whether abnormal midwall fractional shortening predicts either subnormal LV functional reserve or extracardiac damage in asymptomatic hypertensive patients. Accordingly, we compared radionuclide cineangiographic LV ejection fraction at rest and maximum exercise as well as clinical findings between 89 patients with normal and 16 patients with subnormal midwall fractional shortening by echocardiogram. Patients with low midwall fractional shortening were similar in gender, age, and systolic BP to those with normal shortening but had higher mean diastolic BP and body mass indexes (both p < 0.05). The 2 groups also had similar resting ejection fraction (56 +/- 9% vs 55 +/- 15%, with normal or subnormal shortening, respectively, p = NS). Patients with subnormal midwall fractional shortening had higher LV mass and tended to have higher urinary protein excretion and serum creatinine levels. Subnormal LV ejection fraction with exercise (< 54%) was observed in 13 of 89 patients (15%) with normal midwall fractional shortening but in 7 of 16 patients (44%) with subnormal shortening (p < 0.05). Multiple linear regression analysis revealed that midwall fractional shortening independently predicted exercise performance (p < 0.001). Thus, subnormal midwall fractional shortening predicts depressed LV fractional reserve in asymptomatic hypertensive patients and may contribute to identification of patients with extracardiac target-organ damage.

Adult↗
PubMed1996

Rhythm annotation and interobserver reproducibility of measures of heart rate variability.

Interobserver reproducibility is high for time domain and power spectral measures of heart rate variability, with greater reproducibility for low-frequency measures, and especially for the standard deviation of the 5-minute RR intervals over 24 hours, than for high-frequency measures. Overall interobserver variability of < 8% for these measures is largely (50% to 75%) explained by interobserver differences in annotation of supraventricular ectopy and sinus arrhythmia.

Adult↗
PubMed1996

Combined rest and exercise electrocardiographic repolarization findings in relation to structural and functional abnormalities in asymptomatic aortic regurgitation.

The relationship of combined rest and exercise electrocardiographic (ECG) repolarization abnormalities to left ventricular geometry and function was examined in 48 patients with asymptomatic chronic pure aortic regurgitation and no recent use of digitalis. Echocardiographic and radionuclide cineangiographic findings were compared in groups defined by the presence or absence of the "strain" pattern of repolarization abnormality on the resting ECG and also by the presence or absence of standard positive repolarization changes during upright treadmill exercise ( > 0.1 mV additional horizontal or downsloping ST depression). These hierarchic groups demonstrated trends toward progressively abnormal left ventricular dimensions, mass, wall stress, and change in ejection fraction with exercise. Although the presence of the strain pattern on the resting ECG alone was most strongly correlated with underlying functional and geometric abnormalities, an abnormal exercise test response was independently associated with abnormal left ventricular systolic dimension. The large group of patients with no symptoms and normal resting repolarization had only 0% to 4% prevalences of markedly increased systolic dimension (> 55 mm), reduced ejection fraction at rest (< 45%), or reduced ejection fraction during exercise (< 40%), whereas the small group of patients with abnormal resting repolarization and a positive exercise test response had 50% to 83% prevalences of these findings. These data suggest a possible role for rest and exercise ECG in the serial evaluation of patients with aortic regurgitation.

Adult↗
PubMed1996

Biodistribution and autoradiographic localization of I-125--labeled synthetic Peptide in aortic atherosclerosis in cholesterol-fed rabbits.

I-125 labeled SP4 is a synthetic oligopeptide derived from apolipoprotein B of low-density lipoprotein that has been shown to localized in atherosclerotic plaques in experimental animals. However, its biodistribution and mechanism of localization need to be further elucidated. Twenty-four cholesterol-fed (CF) and 20 normal (NL) New Zealand White rabbits were injected with I-125-SP4 and killed 15 to 30 min (6 NL; 6 CF) or 2 h (14 NL; 18 CF) later. We obtained aortic autoradiograms and activity concentrations (% injected dose/gm) in aortic segments and other tissues. The uptake of I-125-SP4 was higher in CF than in NL rabbits in all aortic segments (p < 0.05). I-125-SP4 was cleared rapidly in both CF and NL rabbits with 60 to 70% of the injected dose cleared from the blood by 1 h. No statistically significant differences in radiotracer biodistribution were observed between NL and CF rabbits although activity tended to be higher in the liver, gallbladder, and intestine in NL rabbits and in the kidney and spleen in CF rabbits. Silver grains were distributed mainly on foam cells of the fatty streaks in aortic microautoradiograms from two additional rabbits that had been injected with I-125-SP4. There were 23,518 plus minus 15,878 (SD) grains/mm(2) in fatty plaques but only 14,669 plus minus 11,035 grains/mm(2) in media muscle (p < 0.0001 [9 sections, 17 areas evaluated] in an atherosclerotic animal) in injected animals and 13,439 plus minus 5,565 grains/mm(2) in media muscle (two sections, four areas) in the normal control animals (NS versus media of atherosclerotic animal). I-125-SP4 specifically localizes in aortic atherosclerotic plaques in CF rabbits. There is no significant difference in tissue distribution between normal and CF rabbits except in the aorta. Preliminarily, it appears that the site of tracer uptake is on foam cells and this suggests the possibility of relative specificity for fatty plaque.

Journal Article↗